ISSN 1866-8836
Клеточная терапия и трансплантация
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This paper was presented at the dedication symposium of the new research laboratories of Merck Sharp and Dohme in New York, May, 1966. Columbia University College of Physicians and Sur­geons was a joint sponsor. All the papers presented will be published in book form by Merck & Co. Cost of publication of this article has been covered by the National Foundation.

It seems particularly fitting, in this symposium, to try to assess the prob­able and possible impact of molecular biology and its important com­ponent, the structure and function of nucleic acids, on the future of medicine. Although I attempt specific predictions with considerable trepi­dation, not being qualified in either fortunetelling or medicine, I do so in the firm belief that the findings and concepts of molecular biology will play a leading role in the future of medicine. Medicine, after all, primarily involves the application of biological concepts and understanding to the health and welfare of man.

After considering various alternative presentations, I have decided first to point out some of the principal problem areas facing medical science in which molecular biology is most immediately concerned. I will then do my best to predict some developments in these areas over the next ten to twenty years.

Before doing this, however, I feel a real obligation to mention a prob­lem that is peripheral in one sense, but that in another is related to and even supersedes most others in basic importance to man. This is the world problem of population and the means of arriving at and maintaining an effective balance between the population explosion and natural resources. Although this problem is outside the main thread of this symposium, it is actually of primary importance. Unless it can be solved, and a new "dark age" avoided, scientific progress can hardly be maintained, and the appli­cation to man of new findings will be defeated by sheer numbers.

However, let us assume that this problem will be solved, and proceed to problem areas in medical science. Some of the most important of these are being discussed by the other symposium speakers, auto-immune dis­eases by Sir Macfarlane Burnet, brain function by

Dr. Schmitt, and de­generative diseases by Sir George Pickering. Accordingly, I will concen­trate primarily on the following areas in which progress seems to me to be particularly directly related to the concepts of molecular biology and dependent on nucleic acid research.

These major areas are:

(1) viruses and virus diseases;

(2) hereditary metabolic defects, enzymatic, and regulatory;

(3) developmental, congenital, and structural defects; and

(4) cancer.

What developments can be predicted in these general areas during the next twenty years or so?

In the field of viruses and viral diseases, it can be anticipated fairly confidently that the study of viruses ­­– bacterial, plant, and
animal – will continue to hold as important a place in molecular biology and genetics as has been true during the past decade or so. Most, if not all, viral diseases will be conquered either through immunological means or by the design and synthesis of specific antiviral chemicals. With this, and with definitive understanding of the roles of viruses in human problems involving de­velopment and with regulation of cell growth, will come effective pre­vention and hence control of human problems attributable to viral disease. Finally, it can be anticipated that viruses will be effectively used for man's benefit, in theoretical studies in somatic-cell genetics and possibly in genetic therapy.

In the area of metabolic disorders, the recognition of the genetic basis of many more disorders can be anticipated. The specific enzymatic defects will be identified in many more instances, as already has been done for PKU (phenylketonuria), galactosemia, certain amino acidurias, and ab­normalities in hemoglobin and other serum proteins. Rapid, simple, and sensitive methods for the detection of carriers and for the early diagnosis of affected individuals will be developed, thus facilitating both more effec­tive eugenic measures and more effective therapy by dietary and other means. We can even be somewhat optimistic on the long-range possibility of therapy by the isolation or design, synthesis, and introduction of new genes into defective cells of particular organs.

In the field of developmental biology, as the consequence of a better understanding of the molecular and spatial-temporal sequences involved in differentiation and development, we can foresee the effective prevention and alleviation of developmental errors, such as congenital malformations, whether these be due to genetic defects or to faulty gene expression or regulation or are indirectly related to gene activity via hormone produc­tion or target-organ receptivity.

Perhaps in no area is the foreseeable rapid accumulation of basic infor­mation more pertinent to molecular biological research and concepts, or more promising for the future, than in the area of neoplasia – cancer. I feel that we can reasonably anticipate that the basic causes of many, if not all, forms of cancer will be established within the next few decades. All suspected causes, viral, mutational, or regulatory failures, center on cell genetics, and on nucleic acid structure and function. Hence, we can be reasonably optimistic of the development, first, of effective preventive measures and, later, of curative therapy. These will come by epidemiological, immunological, and chemotherapeutic means, by modification and regulation of gene activities, or by means of gene repair or replace­ment.

Let us now explore the basis for my optimism, which rests, first, on the general validity of the concepts of molecular biology and the significance of nucleic acid structure and function therein and, second, on the "state of the art" in nucleic acid research and on the exponential rate at which knowledge in this and other areas of biology is increasing.

It is now generally accepted that the basic unit of heredity in all forms of life is DNA, deoxyribonucleic acid, consisting of the now familiar complementary stranded double helix of Watson and Crick. This struc­ture uniquely possesses all the qualifications essential for genetic function: specificity through purine and pyrimidine base sequence; mutation through alterations in base sequence; replication by the enzymatic assem­bly of new strands on the two parental strands as templates; and translation into cell function by transcription of one strand into a complementary strand of messenger RNA (ribonucleic acid). The messenger RNA is transferred from the nucleus to the cytoplasm and there directs the as­sembly of amino acids into enzymes and other proteins in the ribosomes, with the sequence of base triplets in the gene thus specifying a particular sequence of amino acids in the protein product.

The past several years have seen the fleshing out of these bare conceptual bones in considerable detail and with some remarkable observations and phenomena.

Genetic material is frequently, or even perhaps usually, present in the form of circular molecules, such as in bacterial "chromosomes" in bacteriophages, in polyoma virus, and perhaps even in chromosomes of higher forms. It would appear that this circularity has a control function in the replication process, which, at least in bacteria, appears to start at a particular location and proceed in one direction at a single growing point which moves along the chromosome until all the genes have been copied and the process is completed [1]. The circularity may also serve in part to protect DNA from enzymatic attack on free ends of the molecule.

The evidence suggests that a double helical form of nucleic acid is es­sential for its replication. For example, replication of a single-stranded phage DNA (ΦX174), of single-stranded RNA of the phage f2, and of several plant and animal viruses has been shown to involve the enzymatic formation of a double-stranded replicative form. Only one of these (-strand), the complement to the parental strand, would then serve as template for the synthesis of new viral RNA (+strand). An apparent exception to the requirement for replication of a double-stranded struc­ture, the in vitro replication of a biologically active bacterial virus RNA, was recently reported by Spiegelman and co-workers [2]. However, later experiments by Weissman and Feix [3] strongly suggest the presence of a double-stranded replicating form of RNA in this system as well.

Strandedness would appear also to be important in repair of damaged DNA, as with ultraviolet radiation. It should be recalled that ultraviolet-produced thymine dimers are split in photoreactivation but are excised and the strand repaired in a dark reaction. Bacterial mutants deficient in the excision reaction are known, and the ultraviolet-damaged double-stranded replicative form of ΦX174 is capable of dark repair, whereas the single-stranded form of the bacteriophage DNA is not. Incidentally, it might also be pointed out here that exo-nuclease III may well be involved in the excision reaction and therefore might be absent in the "excision negative" bacterial mutants just mentioned.

Strandedness and circularity seem also to be important in determining the template specificity in RNA synthesis on either DNA or RNA tem­plates. In vitro, cellular RNA polymerase can use either DNA or RNA templates, either single or double stranded. With double-stranded DNA, both strands usually serve as templates. However, in in vivo m-RNA synthesis and in vivo synthesis of viral RNA, only one of the double strands of the nucleic acid appears to serve as template. This also seems to be true in vitro in several other instances involving transcription to RNA of double-stranded nucleic acids related to bacterial viruses. That circu­larity may be involved in determining single-strand transcription is sug­gested by the experiments of Hayashi, Hayashi, and Spiegelman [4] with ΦX174 replicating form DNA. In vitro, only one strand of the circular form was transcribed, but both strands of the open linear form were so used.

In connection with the structure of DNA and its transcription, an im­portant field of investigation was initiated a few years ago with the dis­covery by Reich and co-workers that actinomycin D primarily acts by binding specifically to the amino group of guanine in the minor groove of double-stranded DNA. In so doing, it prevents the DNA from func­tioning as a template for cellular RNA synthesis but does not affect RNA-dependent synthesis of viral RNA [5]. Other studies [6] have shown that chromomycin and related antibiotics react similarly and that ethidium bromide and daunomycin bind to DNA and inhibit its function non-specifically, perhaps, like proflavin, by intercalation between adjacent base pairs. Bhuyan and Smith [7], in similar studies, have shown that nogalo-mycin binds to DNA, probably to either adenine or thymine residues. In contrast, another antibiotic, tubercidin, an analogue of adenosine, appar­ently is incorporated into both RNA and DNA [8], as are some other base analogues. Such studies in general not only provide an understanding of the molecular basis of activity of these antibiotics but lead to the recog­nition and use of valuable tools in investigating the structure and function­ing of nucleic acids.

The second step of gene transcription involves not only m-RNA but two other classes of RNA, both of which are gene determined. Transfer or soluble RNA (s-RNA) attaches activated amino acids at its CCA ter­minal end and transfers them to the growing polypeptide chain in the ribosome, which contains at least two ribosomal structures containing RNA (18S and 23S). Each amino acid is carried by at least one specific s-RNA. Some evidence suggests that the DNA loci responsible for ribo­somal and transfer RNA are bunched and may be transcribed more or less as a group, whereas the loci for m-RNA are more widely and randomly distributed [9].

Each s-RNA has two separate recognition sites, one specific for its ammo add and one specific for the corresponding base triplet or codon on the m-RNA. The first complete base-sequence analysis was reported just this last year by Holley and collaborators for yeast alanine s-RNA [10]. When sequences of other s-RNA molecules are established, as can be anticipated fairly soon, it should be possible to define structurally both recognition sites, the anticodon, and the amino acid recognition site.

The final step in protein synthesis, the assembly of polypeptide chains, takes place in the ribosomes. These consist of two different-sized subunits and function most effectively as aggregates or polysomes, with each ribosome involved in transcription of a different section of the m-RNA mole­cule that holds the ribosomes together in the aggregate. In some instances at least, a single polycistronic m-RNA molecule may code for several polypeptide chains.

Protein synthesis on the ribosome is subject to regulation and control in a number of ways. One of the important recent questions has been the punctuation in the genetic code. Are there start and stop signals? It seems that there are! The start signal for most Escherichia coli proteins appears to be a particular nucleotide sequence which specifies at least N-formyl-methionine, and perhaps even N-formyl-methionyl-alanyl-serine. After completion and release, one or more of the N-terminal groups is enzymatically removed. The evidence for this process comes from the elegant work of Webster, Engelhart, and Zinder [11] on the in vitro synthesis of f2 virus coat protein and from related findings of Adams and Capecchi [12].

That there are also stop signals seems equally probable. These may func­tion in a manner analogous to the termination of peptide synthesis by puromycin, which is added to the growing carboxyl end of the chain, stopping further additions and causing release of the incomplete chain from the ribosome. At least two possible nucleotide triplets (UAG and UAA), which seem not to code for any ammo acid, have been suggested by Sarabhai, Stretton, Brenner, and Bolle [13] as giving a signal for peptide chain termination in some strains of E. coli.

Ribosomal protein synthesis in vitro can also be modified by conditions or substances that bind to ribosomes, disassociate their subunits, or otherwise affect their structure or binding of s-RNA. Examples are basic com­pounds, such as spermidine, and the antibiotics lincomycin and, probably, chloramphenicol. Interestingly, organic solvents such as alcohol and cer­tain salts may change the specificity of recognition between m-RNA codon and the s-RNA anticodon. Related to this is the finding that sup­pressor mutations may involve alterations in the recognition site of a particular s-RNA and thus restore normal transcription. Another very important related finding is the discovery by Davies, Gilbert, and Gorini [14] that streptomycin alters the specificity of m-RNA codon recognition by s-RNA, and hence disarranges normal transcription, but can function as a "suppressor substance" in correcting faulty transcription due to gene mutation.

In view of the widespread interest in and knowledge of the intricacies of the triplet genetic code, it should here suffice to point out that, as the result of the brilliant pioneering work of Nierenberg, Ochoa, and Khorana, and their collaborators, we now have an almost complete key to the triplet codons for all amino acids. This accomplishment has required particularly the techniques of nucleic acid chemistry and biochemistry, in producing the necessary oligonucleotides of defined sequence and length. I would only remind you, in addition, that the universality of the code has now been fairly convincingly established by work with viruses, bacteria, plants, and animals. This is particularly pertinent to our later consideration of genetic engineering.

Another area of nucleic acid research that should be mentioned here is that of mutation, which in its simplest form represents the substitution of one base for another in a DNA triplet. We already know that certain sub­stitutions are more frequent than others and can selectively be made still more frequent by the incorporation into DNA of base analogues which alter base pairing specificities or, under more natural conditions, by the presence of a "mutator" gene. These observations, together with knowl­edge of the code, make the prospects of directed mutation somewhat more hopeful for the future.

We perhaps should here also remind ourselves that genes and gene functions in living organisms are not isolated entities and phenomena in a test tube but are subject to regulation or control mechanisms which turn them on, or turn them off, either separately or in operon groups, in feed­back response to repressor or activator molecules. Developmental geneticists believe that gene activation and repression are of primary significance in processes of differentiation and development. The more we learn about these repressors and activators and how they work, the more optimistic we can be about the prospects of controlling and correcting faulty develop­mental processes.

Finally, in this general discussion, both for aesthetic completeness and because of its possible role in infective processes and in development, I want to mention extrachromosomal inheritance. The last few years have seen a considerable clarification of the physical basis of extrachromosomal genetic phenomena. Cell organelles such as mitochondria and plastids, and entities such as infective bacterial episomes, replicate and divide inde­pendently of the nucleus, can mutate, and control certain typical charac­teristics of the cells in which they exist. These characteristics are inherited in a non-Mendelian pattern, often completely maternally. It is intellectual­ly satisfying that all such entities investigated have been found to contain double-stranded, helical, high-molecular-weight DNA. It is particularly gratifying to me that it is now known that Neurospora mitochondria grow and divide [15], that they contain DNA [16], and that a cytoplasmic char­acter in Neurospora is transmitted from cell to cell by pure isolated mito­chondria, as shown in our laboratories [17]. Drs. Luck and Reich have most recently [18] produced evidence consistent with the semiconservative replication of Neurospora mitochondrial DNA, as is true for bacterial plant, animal, and some viral DNA. They have also shown, as followed by a species-specific density difference, that this mitochondrial DNA is in­herited maternally. A role of mitochondrial DNA in maternally inherited respiratory-deficient mutants of Neurospora has very recently been sug­gested by Woodward and Munkres [19] to involve the control of mito­chondrial structural protein. It is of considerable interest that chemothera­py is of potential value in controlling the replication of extrachromosomal DNA, as suggested by the effects of agents such as proflavin, streptomy­cin, and nitrosoguanidine in micro-organisms.

In the light of the foregoing survey of some of the high spots of nucleic acid research pertinent to molecular biology, let us refocus our attention on my earlier predictions as to the future of medicine. I hope that I have succeeded in making clear, first, the central role played by nucleic acids in biology and genetics, so that the basic phenomena in the various problem areas, virus infection, metabolic diseases, developmental defects, and neoplasia, are actually interrelated, and, second, the fact that these basic phenomena involve changes from normality because of interference with, or changes in, the normal sequences of molecular biology that link gene to enzyme.

Virus infection introduces new genetic material and interferes with the functioning of host genes. Mutation changes genes, generally for the worse, as in inborn metabolic diseases characterized by single enzyme defects.

Developmental defects may be due to mutant genes, as for clubfoot, harelip, etc.; to virus infection, as with Rubella or probably adenovirus; to drugs such as actinomycin or thalidomide; or to prenatal environmental factors such as a riboflavin deficiency. Some of these environmental fac­tors probably act by changing the spatial-temporal sequence of gene acti­vation and expression necessary for normal development. Certain de­velopmental defects may be due to an extra chromosome as in mongolism or Turner's and Klinefelter's syndromes. These chromosomal effects ap­pear to be due to defective gene expression as the consequence of chromo­some imbalance. It is of considerable interest that some recent data on mongolism in Australia support the possibility that some unknown in­fective agent may affect oogenesis, causing the non-disjunction that leads to the extra chromosome 21. If this proves to be true, the significance for preventive therapy is obvious.

Certain heritable developmental abnormalities are accompanied by and even attributable to hormone deficiencies, as for thyroxin in cretinism or growth hormone in a type of dwarfism. The basis of hormone activity itself is still unsettled. However, evidence has been accumulating recently that many, particularly the sex hormones and the insect hormone ecdy-sone, act by regulating gene activity in the target cells, leading to the production of specific m-RNA, as shown for animals by the recent experi­ments of Kidson and Kirby [20]. It should be pointed out, however, that other modes of action have not been ruled out, for instance, that cell-membrane permeability is involved.

The last area I have emphasized, that of neoplasia or cancer, is at the same time one of the greatest problems facing medicine and one of the most complex. In an intellectual sense this complexity, centering on the variety of phenomena implicated in the causation and manifestations of cancer, is reason for optimism, since it provides the opportunity of understanding the process of caremogenesis, "spontaneous," viral, or chemically or physically induced. All of these would appear basically to involve genetic material. Similarly, there is cause for optimism in understanding and treating the manifestations, since they would appear to involve various steps in gene expression.

This general thesis is supported by the increasing evidence that many forms of cancer in animals are indeed due to particular viruses in a phenomenon basically analogous to lysogenesis in bacteria. Most simply it would appear that viral genes so introduced are integrated into the host-cell genome, transforming them into tumor cells, with characteristic new properties such as loss of contact inhibition, change of morphology and growth requirements, and new tumor or viral antigens. We are coming closer to the clarification of the role of viruses in human cancer through detailed studies of the “transformation" process in cultured cells, induced by human and annual viruses; through studies showing the need for a “helper” virus acting with a tumor vims in viral caremogenesis in animals; and through epidemiological and other studies in human cancer such as malignant lymphoma and leukemia.

The possibilities of prevention and therapy would seem to be many and diverse, ranging from prevention of infection, replication, expression, and integration of viral genetic material, perhaps as with antiviral agents such as HBB, guanidine, and IUDR, to specific chemotherapeutic suppression of the transformed tumor cells, or even their reconversion to normality. Effective attacks on these fronts will lean heavily on our knowledge of the molecuar events involved, that is, on knowledge in molecular and nucleic acid biology.

Many, including myself, have talked and written about the application of the newer knowledge of molecular genetics and biology to the improvement of man’s life, heritage, and health in terms of engineering. In these terms, eugenic engineering operates at the level of existing genes and involves purposeful, conscious effort to decrease the prevalence and expression of undesirable genes. These efforts will be effective in proportion to the numbers of detrimental genes that can be identified; to the development of effective methods for their detection in the hidden, carrier state; and, most important, to the general acceptance by individuals of their social responsibility not to perpetuate these genes.

Eugenic engineering operates at the level of gene expression on the phenotype of the individual. It is already widely used in medicine, if not so recognized, as in the administration of vitamins, hormones such as insulin, and thyroxine. Better-recognized examples include the prevention of the harmful accumulation of toxic materials associated with genetic defects by dietary restrictions such as of phenylalanine in PKU, of galactose in galactosemia, or of certain branched amino acids in maple-sugar urine disease or the recently described isovaleric acidemia. Such diseases are of special interest and significance in that they characteristically involve brain function and mental retardation. This, and the known actions of drugs such as LSD, forecast the eventual understanding of the organic basis of other mental illnesses, such as schizophrenia, and their successful treatment.

Another much less developed type of eugenic engineering would make use of the concepts of gene regulation and control, by way of feedback regulation by the administration of compounds yet to be discovered. For example, the activities of harmful dominant genes in theory could be re­pressed as desired, or inactive genes could be turned back on or derepressed as needed, even in utero at critical periods of development. As already pointed out, hormore therapy may actually represent this type of gene regulation.

I would define genetic engineering as the alteration of existing genes in an individual. This could be accomplished by directed mutation or by the replacement of existing genes by others. In principle, and in respect to possible ways of accomplishing this replacement, there are only minor technical differences between genetic engineering as applied to genes in germinal and in somatic cells, although the net result would be consider­ably different. Precedents for the introduction or transfer of genes from one cell to another exist in microbial systems and are now being tried with mammalian cells in culture. Isolated DNA as such is physically taken up and integrated into the recipient bacterial genome in the transformation process, or in transduction is transferred from one bacterium to another by a virus, followed by integration. If this can be done successfully with animal cells, it will facilitate the development of a mammalian somatic-cell genetics. It will also bring us considerably closer to successful genetic engineering. It is pertinent to point out that, for the phenotypic correction of most genetic errors, only one of the two inactive genes in a diploid cell need be replaced by an active gene and that this may need to be done only in a certain critical number of cells in the particular organ in which the gene function is needed. Hence, it can be suggested that the first successful genetic engineering will be done with the patient's own cells, for example, liver cells, grown in culture. The desired new gene will be introduced, by directed mutation, from normal cells of another donor by transduction or by direct DNA transfer. The rare cell with the desired change will then be selected, grown into a mass culture, and reimplanted in the patient's liver. The efficiency of this process and its potentialities may be consider­ably improved by the synthesis of the desired gene according to the specifications of the genetic code and of the enzyme it determines, by in vitro enzymatic replication of this DNA, and by increasing the effectiveness of DNA uptake and integration by the recipient cells, as we learn more about the factors and conditions affecting these processes.

An even more speculative biological possibility for genetic engineering may be suggested, stemming from the finding by Harris [21] that in culture, mammalian cells, even from different species, can be caused to fuse by exposure to an as yet unidentified component of certain animal viruses. These "hybrid" cells can survive and grow, retaining all or part of the chromosome complements of the two "parental" cells. The possible applicability of this approach to the introduction of new genetic material for purposes of genetic engineering seems obvious.

Let me now try to summarize. I have attempted to point out and discuss some of the high spots in molecular biology and nucleic acid research that are particularly promising for the future of medicine. It is apparent that multidisciplmary concepts, approaches, and techniques are essential to the fulfilment of the potentialities which can now be only speculated on. This is particularly apparent if we try to list some of the areas and techniques involved and indicate some needs for further information and development.

One major area involves the design and synthesis of compounds for chemotherapeutic use. In relation to viruses, these will include agents affecting their adsorption, penetration, and replication. In relation to gene function, transcription to m-RNA, and protein, agents already exist and more surely can be designed that will even more specifically affect DNA and RNA structure and particular functions. Other "suppressor sub­stances" can be imagined, which, like streptomycin, will change nucleic acid transcription at the level of protein synthesis and thereby correct genetic errors. Still others, patterned after repressor or regulator substances yet to be isolated and identified, will be able to modulate the activities of specific genes.

With the structures of key enzymes established, the DNA code com­pletely established, and with suitable synthetic methods available, genes can be synthesized to order. The time may soon come when a few mole­cules of such synthetic genes, or of genes isolated in pure state from na­ture, will be replicated enzymatically in vitro. With more complete knowledge of the biological processes and techniques involved in DNA uptake and integration, these DNA’s can be incorporated into chromo­somes. Genetic engineering will then be just around the corner.

Such speculations as these may be considered by some as too idle day­dreaming for a serious symposium. Yet the phenomena of molecular bi­ology which are now almost taken for granted were not even dreamed of a very few years ago! So, to paraphrase,

The time has come, it may be said,
To dream of many things;
Of genes – and life – and human cells –
Of Medicine – and kings –

References

1. KG Lark. Regulation of chromosome replication and segregation in bacteria. Bacteriol Rev. 1966 Mar;30(1):3-32.

2. S Spiegelman, I Haruna, IB Holland, G Beaudreau, and D Mills. The synthesis of a self-propagating and infectious nucleic acid with a purified enzyme. Proc Natl Acad Sci USA. 1965 Sept; 54(3):919–927.

3. C Weissman and G Feix. Replication of viral RNA. XI. Synthesis of viral "minus" strands in vitro. Proc Natl Acad Sci USA. 1966 May;55(5):1264-8.

4. M Hayashi, MN Hayashi, and S Spiegelman. DNA CIRCULARITY AND THE MECHANISM OF STRAND SELECTION IN THE GENERATION OF GENETIC MESSAGES. Proc Natl Acad Sci USA. 1964 Feb;51:351-9.

5. E Reich. Symp. Soc. Gen. Microbiol., 16:266, 1966.

6. DC Ward, E Reich, and IH Goldberg. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(689):1259-63.

7. BK Bhuyan and CG Smith. Differential interaction of nogalamycin with DNA of varying base composition. Proc Natl Acad Sci USA. 1965 Aug;54(2):566-72.

8. G Acs, E Reich, and M Mori. BIOLOGICAL AND BIOCHEMICAL PROPERTIES OF THE ANALOGUE ANTIBIOTIC TUBERCIDIN. Proc Natl Acad Sci USA. 1964 Aug;52:493-501.

9. BJ McCarthy and ET Bolton. INTERACTION OF COMPLEMENTARY RNA AND DNA. J Mol Biol. 1964 Feb;8:184-200.

10. RW Holley, et al. STRUCTURE OF A RIBONUCLEIC ACID. Science. 1965 Mar 19;147:1462-5.

11. RE Webster, DL Engelhardt, and ND Zinder. In vitro protein synthesis: chain initiation. Proc Natl Acad Sci USA. 1966 Jan;55(1):155-61.

12. J Adams and MR Capecchi. N-formylmethionyl-sRNA as the initiator of protein synthesis. Proc Natl Acad Sci USA. 1966 Jan;55(1):147-55.

13. AS Sarabhai, AO W Stretton, S Brenner, and A Bolle. CO-LINEARITY OF THE GENE WITH THE POLYPEPTIDE CHAIN. Nature. 1964 Jan 4;201:13-7.

14. J Davies, W Gilbert, and L Gorini. STREPTOMYCIN, SUPPRESSION, AND THE CODE. Proc Natl Acad Sci USA. 1964 May;51:883-90.

15. DJL Luck. Genesis of itochondria in neurospora crassa. Proc Natl Acad Sci USA. 1963 Feb 15;49:233-40.

16. DJL Luck and E Reich. DNA IN MITOCHONDRIA OF NEUROSPORA CRASSA. Proc Natl Acad Sci USA. 1964 Oct;52:931-8.

17. EG Diacumakos, L Garnjobst, and EL Tatum. A cytoplasmic character in Neurospora crassa. The role of nuclei and mitochondria. J Cell Biol. 1965 Aug;26(2):427-43.

18. E Reich and DJL Luck. Replication and inheritance of mitochondrial DNA. Proc Natl Acad Sci USA. 1966 Jun;55(6):1600-8.

19. DO Woodward and KD Munkres. Alterations of a maternally inherited mitochondrial structural protein in respiratory-deficient strains of Neurospora. Proc Natl Acad Sci U S A. 1966 Apr;55(4):872-80.

20. C Kidson and KS Kirby. SELECTIVE ALTERATIONS OF MAMMALIAN MESSENGER-RNA SYNTHESIS: EVIDENCE FOR DIFFERENTIAL ACTION OF HORMONES ON GENE TRANSCRIPTION. Nature. 1964 Aug 8;203:599-603.

21. H Harris and JF Watkins. HYBRID CELLS DERIVED FROM MOUSE AND MAN: ARTIFICIAL HETEROKARYONS OF MAMMALIAN CELLS FROM DIFFERENT SPECIES. Nature. 1965 Feb 13;205:640-6.

" ["~DETAIL_TEXT"]=> string(38804) "

This paper was presented at the dedication symposium of the new research laboratories of Merck Sharp and Dohme in New York, May, 1966. Columbia University College of Physicians and Sur­geons was a joint sponsor. All the papers presented will be published in book form by Merck & Co. Cost of publication of this article has been covered by the National Foundation.

It seems particularly fitting, in this symposium, to try to assess the prob­able and possible impact of molecular biology and its important com­ponent, the structure and function of nucleic acids, on the future of medicine. Although I attempt specific predictions with considerable trepi­dation, not being qualified in either fortunetelling or medicine, I do so in the firm belief that the findings and concepts of molecular biology will play a leading role in the future of medicine. Medicine, after all, primarily involves the application of biological concepts and understanding to the health and welfare of man.

After considering various alternative presentations, I have decided first to point out some of the principal problem areas facing medical science in which molecular biology is most immediately concerned. I will then do my best to predict some developments in these areas over the next ten to twenty years.

Before doing this, however, I feel a real obligation to mention a prob­lem that is peripheral in one sense, but that in another is related to and even supersedes most others in basic importance to man. This is the world problem of population and the means of arriving at and maintaining an effective balance between the population explosion and natural resources. Although this problem is outside the main thread of this symposium, it is actually of primary importance. Unless it can be solved, and a new "dark age" avoided, scientific progress can hardly be maintained, and the appli­cation to man of new findings will be defeated by sheer numbers.

However, let us assume that this problem will be solved, and proceed to problem areas in medical science. Some of the most important of these are being discussed by the other symposium speakers, auto-immune dis­eases by Sir Macfarlane Burnet, brain function by

Dr. Schmitt, and de­generative diseases by Sir George Pickering. Accordingly, I will concen­trate primarily on the following areas in which progress seems to me to be particularly directly related to the concepts of molecular biology and dependent on nucleic acid research.

These major areas are:

(1) viruses and virus diseases;

(2) hereditary metabolic defects, enzymatic, and regulatory;

(3) developmental, congenital, and structural defects; and

(4) cancer.

What developments can be predicted in these general areas during the next twenty years or so?

In the field of viruses and viral diseases, it can be anticipated fairly confidently that the study of viruses ­­– bacterial, plant, and
animal – will continue to hold as important a place in molecular biology and genetics as has been true during the past decade or so. Most, if not all, viral diseases will be conquered either through immunological means or by the design and synthesis of specific antiviral chemicals. With this, and with definitive understanding of the roles of viruses in human problems involving de­velopment and with regulation of cell growth, will come effective pre­vention and hence control of human problems attributable to viral disease. Finally, it can be anticipated that viruses will be effectively used for man's benefit, in theoretical studies in somatic-cell genetics and possibly in genetic therapy.

In the area of metabolic disorders, the recognition of the genetic basis of many more disorders can be anticipated. The specific enzymatic defects will be identified in many more instances, as already has been done for PKU (phenylketonuria), galactosemia, certain amino acidurias, and ab­normalities in hemoglobin and other serum proteins. Rapid, simple, and sensitive methods for the detection of carriers and for the early diagnosis of affected individuals will be developed, thus facilitating both more effec­tive eugenic measures and more effective therapy by dietary and other means. We can even be somewhat optimistic on the long-range possibility of therapy by the isolation or design, synthesis, and introduction of new genes into defective cells of particular organs.

In the field of developmental biology, as the consequence of a better understanding of the molecular and spatial-temporal sequences involved in differentiation and development, we can foresee the effective prevention and alleviation of developmental errors, such as congenital malformations, whether these be due to genetic defects or to faulty gene expression or regulation or are indirectly related to gene activity via hormone produc­tion or target-organ receptivity.

Perhaps in no area is the foreseeable rapid accumulation of basic infor­mation more pertinent to molecular biological research and concepts, or more promising for the future, than in the area of neoplasia – cancer. I feel that we can reasonably anticipate that the basic causes of many, if not all, forms of cancer will be established within the next few decades. All suspected causes, viral, mutational, or regulatory failures, center on cell genetics, and on nucleic acid structure and function. Hence, we can be reasonably optimistic of the development, first, of effective preventive measures and, later, of curative therapy. These will come by epidemiological, immunological, and chemotherapeutic means, by modification and regulation of gene activities, or by means of gene repair or replace­ment.

Let us now explore the basis for my optimism, which rests, first, on the general validity of the concepts of molecular biology and the significance of nucleic acid structure and function therein and, second, on the "state of the art" in nucleic acid research and on the exponential rate at which knowledge in this and other areas of biology is increasing.

It is now generally accepted that the basic unit of heredity in all forms of life is DNA, deoxyribonucleic acid, consisting of the now familiar complementary stranded double helix of Watson and Crick. This struc­ture uniquely possesses all the qualifications essential for genetic function: specificity through purine and pyrimidine base sequence; mutation through alterations in base sequence; replication by the enzymatic assem­bly of new strands on the two parental strands as templates; and translation into cell function by transcription of one strand into a complementary strand of messenger RNA (ribonucleic acid). The messenger RNA is transferred from the nucleus to the cytoplasm and there directs the as­sembly of amino acids into enzymes and other proteins in the ribosomes, with the sequence of base triplets in the gene thus specifying a particular sequence of amino acids in the protein product.

The past several years have seen the fleshing out of these bare conceptual bones in considerable detail and with some remarkable observations and phenomena.

Genetic material is frequently, or even perhaps usually, present in the form of circular molecules, such as in bacterial "chromosomes" in bacteriophages, in polyoma virus, and perhaps even in chromosomes of higher forms. It would appear that this circularity has a control function in the replication process, which, at least in bacteria, appears to start at a particular location and proceed in one direction at a single growing point which moves along the chromosome until all the genes have been copied and the process is completed [1]. The circularity may also serve in part to protect DNA from enzymatic attack on free ends of the molecule.

The evidence suggests that a double helical form of nucleic acid is es­sential for its replication. For example, replication of a single-stranded phage DNA (ΦX174), of single-stranded RNA of the phage f2, and of several plant and animal viruses has been shown to involve the enzymatic formation of a double-stranded replicative form. Only one of these (-strand), the complement to the parental strand, would then serve as template for the synthesis of new viral RNA (+strand). An apparent exception to the requirement for replication of a double-stranded struc­ture, the in vitro replication of a biologically active bacterial virus RNA, was recently reported by Spiegelman and co-workers [2]. However, later experiments by Weissman and Feix [3] strongly suggest the presence of a double-stranded replicating form of RNA in this system as well.

Strandedness would appear also to be important in repair of damaged DNA, as with ultraviolet radiation. It should be recalled that ultraviolet-produced thymine dimers are split in photoreactivation but are excised and the strand repaired in a dark reaction. Bacterial mutants deficient in the excision reaction are known, and the ultraviolet-damaged double-stranded replicative form of ΦX174 is capable of dark repair, whereas the single-stranded form of the bacteriophage DNA is not. Incidentally, it might also be pointed out here that exo-nuclease III may well be involved in the excision reaction and therefore might be absent in the "excision negative" bacterial mutants just mentioned.

Strandedness and circularity seem also to be important in determining the template specificity in RNA synthesis on either DNA or RNA tem­plates. In vitro, cellular RNA polymerase can use either DNA or RNA templates, either single or double stranded. With double-stranded DNA, both strands usually serve as templates. However, in in vivo m-RNA synthesis and in vivo synthesis of viral RNA, only one of the double strands of the nucleic acid appears to serve as template. This also seems to be true in vitro in several other instances involving transcription to RNA of double-stranded nucleic acids related to bacterial viruses. That circu­larity may be involved in determining single-strand transcription is sug­gested by the experiments of Hayashi, Hayashi, and Spiegelman [4] with ΦX174 replicating form DNA. In vitro, only one strand of the circular form was transcribed, but both strands of the open linear form were so used.

In connection with the structure of DNA and its transcription, an im­portant field of investigation was initiated a few years ago with the dis­covery by Reich and co-workers that actinomycin D primarily acts by binding specifically to the amino group of guanine in the minor groove of double-stranded DNA. In so doing, it prevents the DNA from func­tioning as a template for cellular RNA synthesis but does not affect RNA-dependent synthesis of viral RNA [5]. Other studies [6] have shown that chromomycin and related antibiotics react similarly and that ethidium bromide and daunomycin bind to DNA and inhibit its function non-specifically, perhaps, like proflavin, by intercalation between adjacent base pairs. Bhuyan and Smith [7], in similar studies, have shown that nogalo-mycin binds to DNA, probably to either adenine or thymine residues. In contrast, another antibiotic, tubercidin, an analogue of adenosine, appar­ently is incorporated into both RNA and DNA [8], as are some other base analogues. Such studies in general not only provide an understanding of the molecular basis of activity of these antibiotics but lead to the recog­nition and use of valuable tools in investigating the structure and function­ing of nucleic acids.

The second step of gene transcription involves not only m-RNA but two other classes of RNA, both of which are gene determined. Transfer or soluble RNA (s-RNA) attaches activated amino acids at its CCA ter­minal end and transfers them to the growing polypeptide chain in the ribosome, which contains at least two ribosomal structures containing RNA (18S and 23S). Each amino acid is carried by at least one specific s-RNA. Some evidence suggests that the DNA loci responsible for ribo­somal and transfer RNA are bunched and may be transcribed more or less as a group, whereas the loci for m-RNA are more widely and randomly distributed [9].

Each s-RNA has two separate recognition sites, one specific for its ammo add and one specific for the corresponding base triplet or codon on the m-RNA. The first complete base-sequence analysis was reported just this last year by Holley and collaborators for yeast alanine s-RNA [10]. When sequences of other s-RNA molecules are established, as can be anticipated fairly soon, it should be possible to define structurally both recognition sites, the anticodon, and the amino acid recognition site.

The final step in protein synthesis, the assembly of polypeptide chains, takes place in the ribosomes. These consist of two different-sized subunits and function most effectively as aggregates or polysomes, with each ribosome involved in transcription of a different section of the m-RNA mole­cule that holds the ribosomes together in the aggregate. In some instances at least, a single polycistronic m-RNA molecule may code for several polypeptide chains.

Protein synthesis on the ribosome is subject to regulation and control in a number of ways. One of the important recent questions has been the punctuation in the genetic code. Are there start and stop signals? It seems that there are! The start signal for most Escherichia coli proteins appears to be a particular nucleotide sequence which specifies at least N-formyl-methionine, and perhaps even N-formyl-methionyl-alanyl-serine. After completion and release, one or more of the N-terminal groups is enzymatically removed. The evidence for this process comes from the elegant work of Webster, Engelhart, and Zinder [11] on the in vitro synthesis of f2 virus coat protein and from related findings of Adams and Capecchi [12].

That there are also stop signals seems equally probable. These may func­tion in a manner analogous to the termination of peptide synthesis by puromycin, which is added to the growing carboxyl end of the chain, stopping further additions and causing release of the incomplete chain from the ribosome. At least two possible nucleotide triplets (UAG and UAA), which seem not to code for any ammo acid, have been suggested by Sarabhai, Stretton, Brenner, and Bolle [13] as giving a signal for peptide chain termination in some strains of E. coli.

Ribosomal protein synthesis in vitro can also be modified by conditions or substances that bind to ribosomes, disassociate their subunits, or otherwise affect their structure or binding of s-RNA. Examples are basic com­pounds, such as spermidine, and the antibiotics lincomycin and, probably, chloramphenicol. Interestingly, organic solvents such as alcohol and cer­tain salts may change the specificity of recognition between m-RNA codon and the s-RNA anticodon. Related to this is the finding that sup­pressor mutations may involve alterations in the recognition site of a particular s-RNA and thus restore normal transcription. Another very important related finding is the discovery by Davies, Gilbert, and Gorini [14] that streptomycin alters the specificity of m-RNA codon recognition by s-RNA, and hence disarranges normal transcription, but can function as a "suppressor substance" in correcting faulty transcription due to gene mutation.

In view of the widespread interest in and knowledge of the intricacies of the triplet genetic code, it should here suffice to point out that, as the result of the brilliant pioneering work of Nierenberg, Ochoa, and Khorana, and their collaborators, we now have an almost complete key to the triplet codons for all amino acids. This accomplishment has required particularly the techniques of nucleic acid chemistry and biochemistry, in producing the necessary oligonucleotides of defined sequence and length. I would only remind you, in addition, that the universality of the code has now been fairly convincingly established by work with viruses, bacteria, plants, and animals. This is particularly pertinent to our later consideration of genetic engineering.

Another area of nucleic acid research that should be mentioned here is that of mutation, which in its simplest form represents the substitution of one base for another in a DNA triplet. We already know that certain sub­stitutions are more frequent than others and can selectively be made still more frequent by the incorporation into DNA of base analogues which alter base pairing specificities or, under more natural conditions, by the presence of a "mutator" gene. These observations, together with knowl­edge of the code, make the prospects of directed mutation somewhat more hopeful for the future.

We perhaps should here also remind ourselves that genes and gene functions in living organisms are not isolated entities and phenomena in a test tube but are subject to regulation or control mechanisms which turn them on, or turn them off, either separately or in operon groups, in feed­back response to repressor or activator molecules. Developmental geneticists believe that gene activation and repression are of primary significance in processes of differentiation and development. The more we learn about these repressors and activators and how they work, the more optimistic we can be about the prospects of controlling and correcting faulty develop­mental processes.

Finally, in this general discussion, both for aesthetic completeness and because of its possible role in infective processes and in development, I want to mention extrachromosomal inheritance. The last few years have seen a considerable clarification of the physical basis of extrachromosomal genetic phenomena. Cell organelles such as mitochondria and plastids, and entities such as infective bacterial episomes, replicate and divide inde­pendently of the nucleus, can mutate, and control certain typical charac­teristics of the cells in which they exist. These characteristics are inherited in a non-Mendelian pattern, often completely maternally. It is intellectual­ly satisfying that all such entities investigated have been found to contain double-stranded, helical, high-molecular-weight DNA. It is particularly gratifying to me that it is now known that Neurospora mitochondria grow and divide [15], that they contain DNA [16], and that a cytoplasmic char­acter in Neurospora is transmitted from cell to cell by pure isolated mito­chondria, as shown in our laboratories [17]. Drs. Luck and Reich have most recently [18] produced evidence consistent with the semiconservative replication of Neurospora mitochondrial DNA, as is true for bacterial plant, animal, and some viral DNA. They have also shown, as followed by a species-specific density difference, that this mitochondrial DNA is in­herited maternally. A role of mitochondrial DNA in maternally inherited respiratory-deficient mutants of Neurospora has very recently been sug­gested by Woodward and Munkres [19] to involve the control of mito­chondrial structural protein. It is of considerable interest that chemothera­py is of potential value in controlling the replication of extrachromosomal DNA, as suggested by the effects of agents such as proflavin, streptomy­cin, and nitrosoguanidine in micro-organisms.

In the light of the foregoing survey of some of the high spots of nucleic acid research pertinent to molecular biology, let us refocus our attention on my earlier predictions as to the future of medicine. I hope that I have succeeded in making clear, first, the central role played by nucleic acids in biology and genetics, so that the basic phenomena in the various problem areas, virus infection, metabolic diseases, developmental defects, and neoplasia, are actually interrelated, and, second, the fact that these basic phenomena involve changes from normality because of interference with, or changes in, the normal sequences of molecular biology that link gene to enzyme.

Virus infection introduces new genetic material and interferes with the functioning of host genes. Mutation changes genes, generally for the worse, as in inborn metabolic diseases characterized by single enzyme defects.

Developmental defects may be due to mutant genes, as for clubfoot, harelip, etc.; to virus infection, as with Rubella or probably adenovirus; to drugs such as actinomycin or thalidomide; or to prenatal environmental factors such as a riboflavin deficiency. Some of these environmental fac­tors probably act by changing the spatial-temporal sequence of gene acti­vation and expression necessary for normal development. Certain de­velopmental defects may be due to an extra chromosome as in mongolism or Turner's and Klinefelter's syndromes. These chromosomal effects ap­pear to be due to defective gene expression as the consequence of chromo­some imbalance. It is of considerable interest that some recent data on mongolism in Australia support the possibility that some unknown in­fective agent may affect oogenesis, causing the non-disjunction that leads to the extra chromosome 21. If this proves to be true, the significance for preventive therapy is obvious.

Certain heritable developmental abnormalities are accompanied by and even attributable to hormone deficiencies, as for thyroxin in cretinism or growth hormone in a type of dwarfism. The basis of hormone activity itself is still unsettled. However, evidence has been accumulating recently that many, particularly the sex hormones and the insect hormone ecdy-sone, act by regulating gene activity in the target cells, leading to the production of specific m-RNA, as shown for animals by the recent experi­ments of Kidson and Kirby [20]. It should be pointed out, however, that other modes of action have not been ruled out, for instance, that cell-membrane permeability is involved.

The last area I have emphasized, that of neoplasia or cancer, is at the same time one of the greatest problems facing medicine and one of the most complex. In an intellectual sense this complexity, centering on the variety of phenomena implicated in the causation and manifestations of cancer, is reason for optimism, since it provides the opportunity of understanding the process of caremogenesis, "spontaneous," viral, or chemically or physically induced. All of these would appear basically to involve genetic material. Similarly, there is cause for optimism in understanding and treating the manifestations, since they would appear to involve various steps in gene expression.

This general thesis is supported by the increasing evidence that many forms of cancer in animals are indeed due to particular viruses in a phenomenon basically analogous to lysogenesis in bacteria. Most simply it would appear that viral genes so introduced are integrated into the host-cell genome, transforming them into tumor cells, with characteristic new properties such as loss of contact inhibition, change of morphology and growth requirements, and new tumor or viral antigens. We are coming closer to the clarification of the role of viruses in human cancer through detailed studies of the “transformation" process in cultured cells, induced by human and annual viruses; through studies showing the need for a “helper” virus acting with a tumor vims in viral caremogenesis in animals; and through epidemiological and other studies in human cancer such as malignant lymphoma and leukemia.

The possibilities of prevention and therapy would seem to be many and diverse, ranging from prevention of infection, replication, expression, and integration of viral genetic material, perhaps as with antiviral agents such as HBB, guanidine, and IUDR, to specific chemotherapeutic suppression of the transformed tumor cells, or even their reconversion to normality. Effective attacks on these fronts will lean heavily on our knowledge of the molecuar events involved, that is, on knowledge in molecular and nucleic acid biology.

Many, including myself, have talked and written about the application of the newer knowledge of molecular genetics and biology to the improvement of man’s life, heritage, and health in terms of engineering. In these terms, eugenic engineering operates at the level of existing genes and involves purposeful, conscious effort to decrease the prevalence and expression of undesirable genes. These efforts will be effective in proportion to the numbers of detrimental genes that can be identified; to the development of effective methods for their detection in the hidden, carrier state; and, most important, to the general acceptance by individuals of their social responsibility not to perpetuate these genes.

Eugenic engineering operates at the level of gene expression on the phenotype of the individual. It is already widely used in medicine, if not so recognized, as in the administration of vitamins, hormones such as insulin, and thyroxine. Better-recognized examples include the prevention of the harmful accumulation of toxic materials associated with genetic defects by dietary restrictions such as of phenylalanine in PKU, of galactose in galactosemia, or of certain branched amino acids in maple-sugar urine disease or the recently described isovaleric acidemia. Such diseases are of special interest and significance in that they characteristically involve brain function and mental retardation. This, and the known actions of drugs such as LSD, forecast the eventual understanding of the organic basis of other mental illnesses, such as schizophrenia, and their successful treatment.

Another much less developed type of eugenic engineering would make use of the concepts of gene regulation and control, by way of feedback regulation by the administration of compounds yet to be discovered. For example, the activities of harmful dominant genes in theory could be re­pressed as desired, or inactive genes could be turned back on or derepressed as needed, even in utero at critical periods of development. As already pointed out, hormore therapy may actually represent this type of gene regulation.

I would define genetic engineering as the alteration of existing genes in an individual. This could be accomplished by directed mutation or by the replacement of existing genes by others. In principle, and in respect to possible ways of accomplishing this replacement, there are only minor technical differences between genetic engineering as applied to genes in germinal and in somatic cells, although the net result would be consider­ably different. Precedents for the introduction or transfer of genes from one cell to another exist in microbial systems and are now being tried with mammalian cells in culture. Isolated DNA as such is physically taken up and integrated into the recipient bacterial genome in the transformation process, or in transduction is transferred from one bacterium to another by a virus, followed by integration. If this can be done successfully with animal cells, it will facilitate the development of a mammalian somatic-cell genetics. It will also bring us considerably closer to successful genetic engineering. It is pertinent to point out that, for the phenotypic correction of most genetic errors, only one of the two inactive genes in a diploid cell need be replaced by an active gene and that this may need to be done only in a certain critical number of cells in the particular organ in which the gene function is needed. Hence, it can be suggested that the first successful genetic engineering will be done with the patient's own cells, for example, liver cells, grown in culture. The desired new gene will be introduced, by directed mutation, from normal cells of another donor by transduction or by direct DNA transfer. The rare cell with the desired change will then be selected, grown into a mass culture, and reimplanted in the patient's liver. The efficiency of this process and its potentialities may be consider­ably improved by the synthesis of the desired gene according to the specifications of the genetic code and of the enzyme it determines, by in vitro enzymatic replication of this DNA, and by increasing the effectiveness of DNA uptake and integration by the recipient cells, as we learn more about the factors and conditions affecting these processes.

An even more speculative biological possibility for genetic engineering may be suggested, stemming from the finding by Harris [21] that in culture, mammalian cells, even from different species, can be caused to fuse by exposure to an as yet unidentified component of certain animal viruses. These "hybrid" cells can survive and grow, retaining all or part of the chromosome complements of the two "parental" cells. The possible applicability of this approach to the introduction of new genetic material for purposes of genetic engineering seems obvious.

Let me now try to summarize. I have attempted to point out and discuss some of the high spots in molecular biology and nucleic acid research that are particularly promising for the future of medicine. It is apparent that multidisciplmary concepts, approaches, and techniques are essential to the fulfilment of the potentialities which can now be only speculated on. This is particularly apparent if we try to list some of the areas and techniques involved and indicate some needs for further information and development.

One major area involves the design and synthesis of compounds for chemotherapeutic use. In relation to viruses, these will include agents affecting their adsorption, penetration, and replication. In relation to gene function, transcription to m-RNA, and protein, agents already exist and more surely can be designed that will even more specifically affect DNA and RNA structure and particular functions. Other "suppressor sub­stances" can be imagined, which, like streptomycin, will change nucleic acid transcription at the level of protein synthesis and thereby correct genetic errors. Still others, patterned after repressor or regulator substances yet to be isolated and identified, will be able to modulate the activities of specific genes.

With the structures of key enzymes established, the DNA code com­pletely established, and with suitable synthetic methods available, genes can be synthesized to order. The time may soon come when a few mole­cules of such synthetic genes, or of genes isolated in pure state from na­ture, will be replicated enzymatically in vitro. With more complete knowledge of the biological processes and techniques involved in DNA uptake and integration, these DNA’s can be incorporated into chromo­somes. Genetic engineering will then be just around the corner.

Such speculations as these may be considered by some as too idle day­dreaming for a serious symposium. Yet the phenomena of molecular bi­ology which are now almost taken for granted were not even dreamed of a very few years ago! So, to paraphrase,

The time has come, it may be said,
To dream of many things;
Of genes – and life – and human cells –
Of Medicine – and kings –

References

1. KG Lark. Regulation of chromosome replication and segregation in bacteria. Bacteriol Rev. 1966 Mar;30(1):3-32.

2. S Spiegelman, I Haruna, IB Holland, G Beaudreau, and D Mills. The synthesis of a self-propagating and infectious nucleic acid with a purified enzyme. Proc Natl Acad Sci USA. 1965 Sept; 54(3):919–927.

3. C Weissman and G Feix. Replication of viral RNA. XI. Synthesis of viral "minus" strands in vitro. Proc Natl Acad Sci USA. 1966 May;55(5):1264-8.

4. M Hayashi, MN Hayashi, and S Spiegelman. DNA CIRCULARITY AND THE MECHANISM OF STRAND SELECTION IN THE GENERATION OF GENETIC MESSAGES. Proc Natl Acad Sci USA. 1964 Feb;51:351-9.

5. E Reich. Symp. Soc. Gen. Microbiol., 16:266, 1966.

6. DC Ward, E Reich, and IH Goldberg. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(689):1259-63.

7. BK Bhuyan and CG Smith. Differential interaction of nogalamycin with DNA of varying base composition. Proc Natl Acad Sci USA. 1965 Aug;54(2):566-72.

8. G Acs, E Reich, and M Mori. BIOLOGICAL AND BIOCHEMICAL PROPERTIES OF THE ANALOGUE ANTIBIOTIC TUBERCIDIN. Proc Natl Acad Sci USA. 1964 Aug;52:493-501.

9. BJ McCarthy and ET Bolton. INTERACTION OF COMPLEMENTARY RNA AND DNA. J Mol Biol. 1964 Feb;8:184-200.

10. RW Holley, et al. STRUCTURE OF A RIBONUCLEIC ACID. Science. 1965 Mar 19;147:1462-5.

11. RE Webster, DL Engelhardt, and ND Zinder. In vitro protein synthesis: chain initiation. Proc Natl Acad Sci USA. 1966 Jan;55(1):155-61.

12. J Adams and MR Capecchi. N-formylmethionyl-sRNA as the initiator of protein synthesis. Proc Natl Acad Sci USA. 1966 Jan;55(1):147-55.

13. AS Sarabhai, AO W Stretton, S Brenner, and A Bolle. CO-LINEARITY OF THE GENE WITH THE POLYPEPTIDE CHAIN. Nature. 1964 Jan 4;201:13-7.

14. J Davies, W Gilbert, and L Gorini. STREPTOMYCIN, SUPPRESSION, AND THE CODE. Proc Natl Acad Sci USA. 1964 May;51:883-90.

15. DJL Luck. Genesis of itochondria in neurospora crassa. Proc Natl Acad Sci USA. 1963 Feb 15;49:233-40.

16. DJL Luck and E Reich. DNA IN MITOCHONDRIA OF NEUROSPORA CRASSA. Proc Natl Acad Sci USA. 1964 Oct;52:931-8.

17. EG Diacumakos, L Garnjobst, and EL Tatum. A cytoplasmic character in Neurospora crassa. The role of nuclei and mitochondria. J Cell Biol. 1965 Aug;26(2):427-43.

18. E Reich and DJL Luck. Replication and inheritance of mitochondrial DNA. Proc Natl Acad Sci USA. 1966 Jun;55(6):1600-8.

19. DO Woodward and KD Munkres. Alterations of a maternally inherited mitochondrial structural protein in respiratory-deficient strains of Neurospora. Proc Natl Acad Sci U S A. 1966 Apr;55(4):872-80.

20. C Kidson and KS Kirby. SELECTIVE ALTERATIONS OF MAMMALIAN MESSENGER-RNA SYNTHESIS: EVIDENCE FOR DIFFERENTIAL ACTION OF HORMONES ON GENE TRANSCRIPTION. Nature. 1964 Aug 8;203:599-603.

21. H Harris and JF Watkins. HYBRID CELLS DERIVED FROM MOUSE AND MAN: ARTIFICIAL HETEROKARYONS OF MAMMALIAN CELLS FROM DIFFERENT SPECIES. Nature. 1965 Feb 13;205:640-6.

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Rockefeller University, New York, New York

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Э. Л. Тэйтум

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Molecular biology, nucleic acids, and the future of medicine.

Reprinted with Permission of The Johns Hopkins University Press.
Originally published in: Perspectives in Biology and Medicine 10:1 (1966), 19-32.

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Molecular biology, nucleic acids, and the future of medicine.

Reprinted with Permission of The Johns Hopkins University Press.
Originally published in: Perspectives in Biology and Medicine 10:1 (1966), 19-32.

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"If I have seen further, it is by standing on the shoulders of giants." (Sir Isaac Newton)

Over 40 years ago – in May 1966 to be more precise – Edward Tatum, whose hundredth birthday will be remembered in December this year, gave a remarkably farsighted talk on the future of medicine. Tatum was one the founding fathers of the newly emerging field of molecular biology. In 1958 he had won the Nobel Prize for Medicine for his work in the 1930s and 40s with George Beadle on radiation-induced metabolic changes in the mould Neurospora crassa. They demonstrated that genes control metabolic processes by determining the function of specific enzymes. This discovery led to the "one gene one enzyme" hypothesis. The double helical nature of DNA had been discovered only 5 years beforehand, and 1958 was also the year in which everything was pulled together by Crick’s formulation of the central dogma of molecular biology.

Tatum had probably been thinking since then about the impact these new biological concepts would have on the "health and the welfare of man." With the cautious disclaimer that he is not in the business of fortune telling he tries in his talk to predict how these discoveries might change medicine in the "next 10 to 20 years."
To us, who enjoy the benefit of hindsight, it is fascinating to see the outcome of his predictions. Omitting immunology and neuroscience, which were covered in other talks of the same meeting, Tatum is remarkably precise with regard to the directions this new knowledge would lead medical science and also in outlining the therapeutic goals medicine would aspire to reach. Other predictions are less accurate, mostly concerning time scale and complexity.

Certainly, Tatum’s urgent warning at the beginning of the talk about world population growth and the limitation of natural resources has not been heeded. With today’s knowledge, we should also add climate change to these dangers. Even if the dire consequences he predicts have not yet taken full effect we are already seeing them emerge. Unfortunately, the political reactions such as military adventures to secure resources, failed developmental policies not primarily aimed at increasing self sustained and competitive economies in the developing world, and indecisiveness or even simple denial of climate change, have been grossly inadequate responses to these challenges. These warnings are if anything even more urgent today and changes in the political approaches to deal with the underlying problems are more desperately needed than ever.

As he predicted, molecular virology has led to an enormous insight into the biology of many viruses, and consequently to novel and effective therapeutic strategies against viral disease. However, we are still far away from conquering "most if not all" viral diseases. The high mutability of viruses, enabling them to avoid initially effective therapies, could not have been predicted; even less foreseeable was the emergence of new viral diseases, such as HIV, Ebola, or SARS, some of which evolve from animal pathogens. The lesson to be learned is that virus-human interactions are part of our genetic makeup and evolutionary inheritance and will probably always keep us busy and pose new challenges, although constant accumulation of molecular understanding will increase our ability to fight back via prevention and treatment.

Viruses have also become important research tools and, as Tatum anticipated, they can be used to carry therapeutic DNA into affected cells. Long before the techniques of human cell culture and cell expansion had been established, he suggested an ex vivo hepatocyte gene therapy protocol. His presentation is often referenced as one of the very first published predictions of human gene therapy. However, it still took until the early 90s for the first clinical trails to be conducted, and almost 10 years more for the first curative success on X-SCID patients in 1999.

Similarly, without ignoring the great progress in cancer research and therapy which confirms the trend of Tatum’s prediction, the predicted level of understanding of the basic causes of cancer within his timescale appears over-optimistic, despite his recognition of the great complexity of this group of diseases. The emergence of cell biology, which reintegrates the discoveries of molecular biology at the level of the smallest unit of life, the cell, is one of the reactions of biomedical science to reach the aspired goals in the understanding of cancer and other diseases. Today, about 40 years later, the knowledge of molecular and cellular biology, immunology and molecular pharmacology, including gene therapy, all combined in the basic science arsenal of molecular medicine is indeed beginning to provide the anticipated first effective preventive measures and curative therapies.

Despite knowing that mutations are the molecular basis for genetic diseases, it took about 20 more years to develop a strategy for discovering the individual genes and mutations responsible for the majority of these conditions in which the phenotype does not immediately point to a known defective protein. This "reverse genetics" or "positional cloning" strategy was first applied to Chronic Granulomatosis Disease and Duchenne Muscular Dystrophy in 1986, followed in 1989 by Cystic Fibrosis, and in 1990 by Neurofibromatosis I. These gene searches took an international effort over more than 10 years. Nowadays, based on the completion of the human genome project and a battery of genome spanning markers, such gene searches can be done in months or even weeks. These enormous steps forward have only become possible through the earlier development of the in vitro DNA-recombination and molecular cloning technologies in the mid–1970s and 80s.

Tatum’s vision of applying the knowledge of molecular biology to detect disease-causing gene mutations in carriers was realized in the early 80s by DNA diagnosis for many monogenic diseases. Tatum is, no doubt, motivated by a deeply humanistic responsibility in his aim to "improve man’s life, heritage and health". However, the social concept of "eugenic engineering" to make a "conscious effort to decrease the prevalence and expression of undesirable genes" through "most important … general acceptance by individuals of their social responsibility not to perpetuate these genes" should not go unchallenged. Besides the unfortunate use of the historically tainted expression "eugenic", the idea of societal or moral pressure to interfere with individual reproductive decisions for the perceived "greater good of mankind" in the fairly distant future cannot be accepted without comment. We are already seeing that individual genome sequencing is able to provide information on a multitude of undesirable genetic traits. It is likely that every human individual can be shown to carry one or several of them. As is nowadays broadly accepted good practice in DNA diagnostics, great care must be taken to ensure that these data are handled confidentially and that professional genetic counseling is provided to avoid stigmatization and undue anxiety as well as to allow the tested individual to make informed reproductive and/or lifestyle decisions in accordance with their personal choices. Such individual decisions will of course be largely influenced by the prospects of effective or even curative treatments and advances in reproductive medicine. Further improving these fields of medicine is our responsibility in fulfilling Tatum’s humanistic legacy.

Edward Lewis Tatum was one of the scientific giants on whose shoulders we stand in the further development of molecular biology and its application for human health and welfare. The advances in medicine over the last 40 years, as he predicted, have offered and continue to offer new solutions, including gene therapy. Even his vision of curing genetic disease by mutation correction appears now as a realistic goal. If achievable and safe it will be for future generations to decide if this may be a medically justifiable and ethically acceptable approach to correct adverse sequences at the germ line level.

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"If I have seen further, it is by standing on the shoulders of giants." (Sir Isaac Newton)

Over 40 years ago – in May 1966 to be more precise – Edward Tatum, whose hundredth birthday will be remembered in December this year, gave a remarkably farsighted talk on the future of medicine. Tatum was one the founding fathers of the newly emerging field of molecular biology. In 1958 he had won the Nobel Prize for Medicine for his work in the 1930s and 40s with George Beadle on radiation-induced metabolic changes in the mould Neurospora crassa. They demonstrated that genes control metabolic processes by determining the function of specific enzymes. This discovery led to the "one gene one enzyme" hypothesis. The double helical nature of DNA had been discovered only 5 years beforehand, and 1958 was also the year in which everything was pulled together by Crick’s formulation of the central dogma of molecular biology.

Tatum had probably been thinking since then about the impact these new biological concepts would have on the "health and the welfare of man." With the cautious disclaimer that he is not in the business of fortune telling he tries in his talk to predict how these discoveries might change medicine in the "next 10 to 20 years."
To us, who enjoy the benefit of hindsight, it is fascinating to see the outcome of his predictions. Omitting immunology and neuroscience, which were covered in other talks of the same meeting, Tatum is remarkably precise with regard to the directions this new knowledge would lead medical science and also in outlining the therapeutic goals medicine would aspire to reach. Other predictions are less accurate, mostly concerning time scale and complexity.

Certainly, Tatum’s urgent warning at the beginning of the talk about world population growth and the limitation of natural resources has not been heeded. With today’s knowledge, we should also add climate change to these dangers. Even if the dire consequences he predicts have not yet taken full effect we are already seeing them emerge. Unfortunately, the political reactions such as military adventures to secure resources, failed developmental policies not primarily aimed at increasing self sustained and competitive economies in the developing world, and indecisiveness or even simple denial of climate change, have been grossly inadequate responses to these challenges. These warnings are if anything even more urgent today and changes in the political approaches to deal with the underlying problems are more desperately needed than ever.

As he predicted, molecular virology has led to an enormous insight into the biology of many viruses, and consequently to novel and effective therapeutic strategies against viral disease. However, we are still far away from conquering "most if not all" viral diseases. The high mutability of viruses, enabling them to avoid initially effective therapies, could not have been predicted; even less foreseeable was the emergence of new viral diseases, such as HIV, Ebola, or SARS, some of which evolve from animal pathogens. The lesson to be learned is that virus-human interactions are part of our genetic makeup and evolutionary inheritance and will probably always keep us busy and pose new challenges, although constant accumulation of molecular understanding will increase our ability to fight back via prevention and treatment.

Viruses have also become important research tools and, as Tatum anticipated, they can be used to carry therapeutic DNA into affected cells. Long before the techniques of human cell culture and cell expansion had been established, he suggested an ex vivo hepatocyte gene therapy protocol. His presentation is often referenced as one of the very first published predictions of human gene therapy. However, it still took until the early 90s for the first clinical trails to be conducted, and almost 10 years more for the first curative success on X-SCID patients in 1999.

Similarly, without ignoring the great progress in cancer research and therapy which confirms the trend of Tatum’s prediction, the predicted level of understanding of the basic causes of cancer within his timescale appears over-optimistic, despite his recognition of the great complexity of this group of diseases. The emergence of cell biology, which reintegrates the discoveries of molecular biology at the level of the smallest unit of life, the cell, is one of the reactions of biomedical science to reach the aspired goals in the understanding of cancer and other diseases. Today, about 40 years later, the knowledge of molecular and cellular biology, immunology and molecular pharmacology, including gene therapy, all combined in the basic science arsenal of molecular medicine is indeed beginning to provide the anticipated first effective preventive measures and curative therapies.

Despite knowing that mutations are the molecular basis for genetic diseases, it took about 20 more years to develop a strategy for discovering the individual genes and mutations responsible for the majority of these conditions in which the phenotype does not immediately point to a known defective protein. This "reverse genetics" or "positional cloning" strategy was first applied to Chronic Granulomatosis Disease and Duchenne Muscular Dystrophy in 1986, followed in 1989 by Cystic Fibrosis, and in 1990 by Neurofibromatosis I. These gene searches took an international effort over more than 10 years. Nowadays, based on the completion of the human genome project and a battery of genome spanning markers, such gene searches can be done in months or even weeks. These enormous steps forward have only become possible through the earlier development of the in vitro DNA-recombination and molecular cloning technologies in the mid–1970s and 80s.

Tatum’s vision of applying the knowledge of molecular biology to detect disease-causing gene mutations in carriers was realized in the early 80s by DNA diagnosis for many monogenic diseases. Tatum is, no doubt, motivated by a deeply humanistic responsibility in his aim to "improve man’s life, heritage and health". However, the social concept of "eugenic engineering" to make a "conscious effort to decrease the prevalence and expression of undesirable genes" through "most important … general acceptance by individuals of their social responsibility not to perpetuate these genes" should not go unchallenged. Besides the unfortunate use of the historically tainted expression "eugenic", the idea of societal or moral pressure to interfere with individual reproductive decisions for the perceived "greater good of mankind" in the fairly distant future cannot be accepted without comment. We are already seeing that individual genome sequencing is able to provide information on a multitude of undesirable genetic traits. It is likely that every human individual can be shown to carry one or several of them. As is nowadays broadly accepted good practice in DNA diagnostics, great care must be taken to ensure that these data are handled confidentially and that professional genetic counseling is provided to avoid stigmatization and undue anxiety as well as to allow the tested individual to make informed reproductive and/or lifestyle decisions in accordance with their personal choices. Such individual decisions will of course be largely influenced by the prospects of effective or even curative treatments and advances in reproductive medicine. Further improving these fields of medicine is our responsibility in fulfilling Tatum’s humanistic legacy.

Edward Lewis Tatum was one of the scientific giants on whose shoulders we stand in the further development of molecular biology and its application for human health and welfare. The advances in medicine over the last 40 years, as he predicted, have offered and continue to offer new solutions, including gene therapy. Even his vision of curing genetic disease by mutation correction appears now as a realistic goal. If achievable and safe it will be for future generations to decide if this may be a medically justifiable and ethically acceptable approach to correct adverse sequences at the germ line level.

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Профессор генной терапии, Лондонский Имперский Колледж, Великобритания.

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Charles Coutelle

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Emeritus Professor of Gene Therapy, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Molecular and Cellular Medicine Section, SW7 2AZ UK

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13418" ["VALUE"]=> string(75) "From mould to man. Edward Lewis Tatum’s vision of the future of medicine." ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(75) "From mould to man. Edward Lewis Tatum’s vision of the future of medicine." ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13422" ["VALUE"]=> array(2) { ["TEXT"]=> string(17207) "<p class="bodytext">«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)<br /><br />Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.<br /><br />Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.<br /><br />Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо. </p> <p class="bodytext">Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями. </p> <p class="bodytext">Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения. </p> <p class="bodytext">С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой. </p> <p class="bodytext">Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее. </p> <p class="bodytext">Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах. </p> <p class="bodytext">Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума. </p> <p class="bodytext">Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(16995) "

«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)

Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.

Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.

Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо.

Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями.

Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения.

С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой.

Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее.

Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах.

Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума.

Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики.

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Charles Coutelle

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Charles Coutelle

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Emeritus Professor of Gene Therapy, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Molecular and Cellular Medicine Section, SW7 2AZ UK

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Emeritus Professor of Gene Therapy, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Molecular and Cellular Medicine Section, SW7 2AZ UK

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Ш. Кутелль

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Профессор генной терапии, Лондонский Имперский Колледж, Великобритания.

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Профессор генной терапии, Лондонский Имперский Колледж, Великобритания.

" } ["FULL_TEXT_RU"]=> array(37) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13422" ["VALUE"]=> array(2) { ["TEXT"]=> string(17207) "<p class="bodytext">«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)<br /><br />Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.<br /><br />Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.<br /><br />Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо. </p> <p class="bodytext">Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями. </p> <p class="bodytext">Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения. </p> <p class="bodytext">С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой. </p> <p class="bodytext">Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее. </p> <p class="bodytext">Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах. </p> <p class="bodytext">Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума. </p> <p class="bodytext">Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(16995) "

«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)

Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.

Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.

Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо.

Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями.

Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения.

С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой.

Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее.

Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах.

Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума.

Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики.

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«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)

Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.

Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.

Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо.

Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями.

Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения.

С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой.

Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее.

Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах.

Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума.

Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики.

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Introduction

The young field of stem cell research leads to a change of paradigm in the modern medicinal world from a symptomatic to a causal treatment of previously untreatable diseases such as Parkinson’s disease, Diabetes mellitus, and heart failure. In 1998, the first human embryonic stem cell (hESC) lines were established in the USA [1]. It was in 2002 that the combination of somatic cell nuclear transfer (SCNT), ES cell derivation, and gene therapy in a mouse model provided indications for autologous treatment of immune deficiencies in the near future [2]. The reprogramming of adult somatic cells into pluripotent cells was achieved by 2006 [3], marking a milestone with fundamental implications on developmental dynamics, which also challenged the categorization of cells by potency. The first human-induced pluripotent stem cells (hiPSC) via transference of pluripotence-associated genes were produced in Japan [4]. Although hiPSC have already had a great impact on the development of therapeutic strategies, hESC remain the benchmark for characterization of pluripotency. A unifying problem for the research on hESC or hiPSC is the lack of standardized methods and criteria to characterize pluripotency, which are essential for comparing scientific results and controlling the risks in future clinical and diagnostic applications. A harmonized regulatory landscape of stem cell research would promote an environment for the efficient development of internationally accepted standards for pluripotent cells characterization and their donation, handling, and application.

In order to reach this goal it is necessary to make regulations and their current changes known and transparent to the stem cell research community, regulators, and stakeholders. hESCreg provides an efficient tool and central platform for the registration and documentation of human embryonic stem cell (hESC) lines being derived and available to the European Union and beyond [5, 6, 7, 8]. Currently, the registry holds information on more than 700 hESC-lines and several hiPSC-lines (see figure 1). hESCreg is coordinated by the Berlin-Brandenburg Center for Regenerative Therapies (BCRT) and the Center for Regenerative Medicine Barcelona, with  the UK Stem Cell Bank as a lead partner. Community representatives from more than 15 countries act as National Contacts for hESCreg. These are Australia, Belgium, the Czech Republic, China, Denmark, Finland, France, India, Israel, the Netherlands, Spain, Sweden, Switzerland, Turkey, the United Kingdom, and the USA.

Table 1.
Regulatory Variations for Embryonic Stem Cell Research in National Contact countries of hESCreg. Whilst certain countries enable specific legislation on hESC research there may be an effective ban on such research in others. The three different colored sections in the table resemble the three different positions on hESC research in Europe and beyond. For a geographical overview please see Figure 1.

1creation of interspecies embryos allowed,
2
law open to interpretation as regards SCNT,
3compensation for embryo or cell donation,
4not with federal funding as outlined in Dickey-Wicker.

2009-4-en-Elstner-Table1.png

Relevant legislation and its practical interpretation in selected countries

The following section describes the legal situation in countries where a) hESCreg has a National Contact representative, and b) which have been selected due to recent or upcoming changes in their hESC-specific legislation: Australia, China, India, Finland, the Netherlands, Norway, Turkey, UK, and the USA (see also Figure 1 and Table 1).

Figure 1.
The Status of hESC Research Legislation in National Contact countries of hESCreg.
The three different colors resemble the three different positions on hESC research: For a detailed overview please refer to table 1. Dark green: hESC research and derivation of hESC lines from supernumerary IVF embryos permitted, SCNT permitted, Light green: hESC research and derivation of hESC lines from supernumerary IVF embryos permitted, SCNT prohibited, Red: hESC research permitted only with imported hESC lines, hESC derivation and SCNT prohibited. Number of hESC provided = number of hESC lines derived in the respective country.

2009-4-en-Elstner-Figure1-new2.png

Information on hESC legislation in other National Contact countries of hESCreg, such as Belgium, the Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Portugal, Spain, Sweden, and Switzerland can be found in another of our recent publications [6]. In both articles we focus on regulatory issues such as pre-implantation genetic diagnosis (PGD), procurement of embryos for research, research on and derivation of hESC lines from a) supernumerary embryos coming from in-vitro fertilization (IVF) programs and that are no longer intended for clinical use, and b) embryos created for research, i.e. human embryos created by IVF with donated gametes and not intended to induce pregnancy, creation of embryos by SCNT, and the creation of interspecies embryos including cytoplasmic hybrid embryos and hiPSC.

The legislative bases for human embryo and hESC research in Australia are the Act on Prohibition of Human Cloning for Reproduction (2002), and the Act on Research Involving Human Embryos (2002), both being amended in December 2006 and effective from June 2007 on. They allow the creation of IVF and SCNT embryos as well as the derivation of hESC lines from these sources as well as research on hESC lines. PGD is allowed. Further regulatory changes are already expected in 2010.

In China the guidelines on human embryonic stem cell research from 2003, which were amended in March 2009, now allow the creation of supernumerary IVF and SCNT embryos for research. Moreover, PGD is permitted and the use of surplus PGD embryos and interspecies embryos are allowed.

Finland experienced the last amendment of the Medical Research Act 488 from 1999 in November 2009. The production of embryos for research purposes is prohibited. The legislative text is open to interpretation whether the creation of SCNT embryos is permitted or not, since the definition of an embryo refers to a “living group of cells resulting from fertilization”. The creation of an IVF embryo is not regulated in the law but the research on surplus IVF embryos is allowed. Regulation of the research on PGD embryos as well as the derivation of hESC lines from supernumerary PGD or IVF embryos is open to interpretation of the legislative text.

In India the DBT-ICMR guidelines regulate issues on stem cell research but have not become law yet. The creation of embryos by SCNT is allowed, this issue falls under “restricted areas of research” of the DBT-ICMR guidelines. The derivation of hESC lines from supernumerary IVF embryos is allowed, as is the research on embryos and hESC lines.

The Netherlands’ Embryo Act from 2002 was amended in 2007. The creation of embryos solely for research purposes is not allowed. The creation of IVF embryos for research purposes is not allowed. The derivation of hESC lines from supernumerary IVF and SCNT embryos for research is allowed if no other source than embryonic stem cells can be used as an alternative. PGD is allowed. Both, hESC line derivation and PGD must be applied at and approved by the CCMO (Central Committee for Research Involving Human Subjects). There are no further changes expected before 2012.

The Norwegian Biotechnology Act from 2007 was revised in 2008. It does not allow the creation of IVF embryos for research purposes. Research on supernumerary IVF embryos and PGD embryos is allowed. The derivation of hESC from supernumerary IVF embryos and SCNT for medical and biological research is allowed.

In Turkey the act “By-law on centers for in vitro fertilization and embryo transfer” concerning research on human embryos from 1987 was amended in 2005. IVF and PDG are legal in the country. hESC research is not regulated by a specific law. However, the Ministry of Health announced a 2005 memorandum stating that until specific guidelines are established, hESC derivation and research should not be performed in the country. Research with imported hESC lines may be performed. A new act is expected to be announced in 2010. For that, it is expected that hESC derivation for research purposes and hESC research will be regulated and allowed in certain qualified institutions and under certain conditions (such as lines with genetic diseases).

In the United Kingdom the Human Fertilisation and Embryology Act, which became law in 1990, was amended at the end of 2008 and legalizes the creation of embryos (including artificial techniques as SCNT) and the creation of interspecies embryos for research. The derivation of hESC lines from supernumerary IVF, SCNT and interspecies embryos are allowed. The definition of an embryo now includes embryos created by cloning and other processes.

In the USA there are different legal situations with respect to embryo and hESC research. The federal law concerning human embryo and embryonic stem cell (hESC) research is the Dickey-Wicker Amendment of 1995, which was again amended in 2009. The research on hESC lines and the derivation of hESC lines from IVF embryos, from embryos created by SCNT and from human admixed embryos is allowed but not for those projects with federal funding as outlined in the Dickey-Wicker Amendment. NIH-funded research is allowed with NIH-approved cell lines only. The NIH reviews information on informed consent and derivation for each line it registers. Non-federally funded research is reviewed by institutional review boards (IRB/SCRO). Creation of embryos for research must follow an IRB-approved protocol (45 CFR 46.107). In addition, IRB/SCRO committees tend to follow national guidelines such as those established by the National Academies of Science and the ISSCR.

Conclusion

Novel legislation and legislative changes need to take into account scientific progress and must be flexible enough to accommodate novel research results and the subsequent changes in the foundations of ethical views. It is unlikely that there will be a single universally accepted view on the ethical, legal, and moral status of the embryo as such, nor on the use of hESC lines derived thereof [5, 6]. But the recent advances in reprogramming show an enormous dynamic and developmental potential of almost any cell and thus question the basis for defining the embryo only as inherently totipotent. Totipotency is probably not inherent to cells derived from embryos and may become inducible by technical means from any differentiated adult cell, for example through the generation of sperm and oocytes from hiPSC. These questions are not yet or only partially reflected in legislative texts. Japan, for example, has prohibited the use of hiPSC for the creation of human gametes, embryos, and their implantation into animal or human wombs [9, 10]. It is therefore expected that the legislative and regulatory landscape will continue to change and that the pressure for international harmonization and transparency will increase.

An essential requirement is therefore the transparent information of what can be done with hiPSC and hESC. One of the tasks of the hESCreg is the reflection of international pluralism by providing information on each registered cell including its source and characteristics, as well as the ethical provenance [6, 7, 8]. This will be one aspect for safeguarding high standards in relation to ethical concerns and transparency in research. Consequently, the European Commission might use hESCreg as a central reference for all funding decisions on proposed hESC research projects within the Seventh EU Framework Programme.

Furthermore, hESCreg is also involved in providing information to the public about this highly sensitive field of research and its legal framework. By providing transparency an increased acceptance of this work is expected. Future tasks of the registry will include the establishment of a pluripotent stem cell registry at the international level, the inclusion of all types of pluripotent stem cells (hiPSC and others), the integration of a knowledge-service tool, the inclusion of banking service tools, the provision of an open and standardized common forum for exchange, and last but not least the development of guidelines for standards, governance, and ethical procurement of pluripotent stem cells.

References

1. Thomson, JA; Itskovitz-Eldor, J; Shapiro, SS; Waknitz, MA; Swiergiel, JJ; Marshall, VS; Jones, JM. Science. 1998 Nov 6; 282(5391):1145-7. Embryonic stem cell lines derived from human blastocysts. Science 1998 Dec 4; 282(5395):1827.

2. Rideout WM 3rd, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell. 2002 Apr 5; 109(1):17-27.

3. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663-76. Epub 2006 Aug 10.

4. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc. 2007;2(12):3081-9.

5. Cervera RP, Stojkovic M. Developments and Challenges in Human Embryonic Stem Cell Research in Spain. Stem Cell Rev Rep. 2009 Oct 3. [Epub ahead of print]

6. Elstner A, Damaschun A, Kurtz A, Stacey G, Arán B, Veiga A, Borstlap J. The changing landscape of European and international regulation on embryonic stem cell research. Stem Cell Res. 2009 Mar;2(2):101-7. Epub 2008 Nov 17.

7. Borstlap J, Stacey G, Kurtz A, Elstner A, Damaschun A, Arán B, Veiga A. First evaluation of the European hESCreg. Nat Biotechnol. 2008 Aug; 26(8):859-60.

8. Sipp, D., 2008. Q & A: Anna Veiga. Nat Med. 2008 Mar;14(3):234

9. Stocum, D.L. Zupanc G.K. Stretching the limits: Stem Cells in Regeneration Science. Dev Dyn. 2008 Dec; 237(12):3648-71. Review.

10. Cyranoski D. Stem cells: 5 things to know before jumping on the iPS bandwagon. Nature 452: 406-408; 2008.

Acknowledgements

The authors gratefully acknowledge the representatives of the National Contacts of the Human European Stem Cell Registry — hESCreg — for their contributions, input and helpful discussions. Especially we would like to thank Claus Yding Andersen, Necati Findikli, Derek Hei, Maneesha Inamdar, Anna Michalska, Christine Mummery, Timo Otonkoski, Glyn Stacey Benjamin Reubinoff, Arne Sunde and Fanyi Zeng. Many thanks to Luis Huegel for his assistance in layout work.

" ["~DETAIL_TEXT"]=> string(16664) "

Introduction

The young field of stem cell research leads to a change of paradigm in the modern medicinal world from a symptomatic to a causal treatment of previously untreatable diseases such as Parkinson’s disease, Diabetes mellitus, and heart failure. In 1998, the first human embryonic stem cell (hESC) lines were established in the USA [1]. It was in 2002 that the combination of somatic cell nuclear transfer (SCNT), ES cell derivation, and gene therapy in a mouse model provided indications for autologous treatment of immune deficiencies in the near future [2]. The reprogramming of adult somatic cells into pluripotent cells was achieved by 2006 [3], marking a milestone with fundamental implications on developmental dynamics, which also challenged the categorization of cells by potency. The first human-induced pluripotent stem cells (hiPSC) via transference of pluripotence-associated genes were produced in Japan [4]. Although hiPSC have already had a great impact on the development of therapeutic strategies, hESC remain the benchmark for characterization of pluripotency. A unifying problem for the research on hESC or hiPSC is the lack of standardized methods and criteria to characterize pluripotency, which are essential for comparing scientific results and controlling the risks in future clinical and diagnostic applications. A harmonized regulatory landscape of stem cell research would promote an environment for the efficient development of internationally accepted standards for pluripotent cells characterization and their donation, handling, and application.

In order to reach this goal it is necessary to make regulations and their current changes known and transparent to the stem cell research community, regulators, and stakeholders. hESCreg provides an efficient tool and central platform for the registration and documentation of human embryonic stem cell (hESC) lines being derived and available to the European Union and beyond [5, 6, 7, 8]. Currently, the registry holds information on more than 700 hESC-lines and several hiPSC-lines (see figure 1). hESCreg is coordinated by the Berlin-Brandenburg Center for Regenerative Therapies (BCRT) and the Center for Regenerative Medicine Barcelona, with  the UK Stem Cell Bank as a lead partner. Community representatives from more than 15 countries act as National Contacts for hESCreg. These are Australia, Belgium, the Czech Republic, China, Denmark, Finland, France, India, Israel, the Netherlands, Spain, Sweden, Switzerland, Turkey, the United Kingdom, and the USA.

Table 1.
Regulatory Variations for Embryonic Stem Cell Research in National Contact countries of hESCreg. Whilst certain countries enable specific legislation on hESC research there may be an effective ban on such research in others. The three different colored sections in the table resemble the three different positions on hESC research in Europe and beyond. For a geographical overview please see Figure 1.

1creation of interspecies embryos allowed,
2
law open to interpretation as regards SCNT,
3compensation for embryo or cell donation,
4not with federal funding as outlined in Dickey-Wicker.

2009-4-en-Elstner-Table1.png

Relevant legislation and its practical interpretation in selected countries

The following section describes the legal situation in countries where a) hESCreg has a National Contact representative, and b) which have been selected due to recent or upcoming changes in their hESC-specific legislation: Australia, China, India, Finland, the Netherlands, Norway, Turkey, UK, and the USA (see also Figure 1 and Table 1).

Figure 1.
The Status of hESC Research Legislation in National Contact countries of hESCreg.
The three different colors resemble the three different positions on hESC research: For a detailed overview please refer to table 1. Dark green: hESC research and derivation of hESC lines from supernumerary IVF embryos permitted, SCNT permitted, Light green: hESC research and derivation of hESC lines from supernumerary IVF embryos permitted, SCNT prohibited, Red: hESC research permitted only with imported hESC lines, hESC derivation and SCNT prohibited. Number of hESC provided = number of hESC lines derived in the respective country.

2009-4-en-Elstner-Figure1-new2.png

Information on hESC legislation in other National Contact countries of hESCreg, such as Belgium, the Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Portugal, Spain, Sweden, and Switzerland can be found in another of our recent publications [6]. In both articles we focus on regulatory issues such as pre-implantation genetic diagnosis (PGD), procurement of embryos for research, research on and derivation of hESC lines from a) supernumerary embryos coming from in-vitro fertilization (IVF) programs and that are no longer intended for clinical use, and b) embryos created for research, i.e. human embryos created by IVF with donated gametes and not intended to induce pregnancy, creation of embryos by SCNT, and the creation of interspecies embryos including cytoplasmic hybrid embryos and hiPSC.

The legislative bases for human embryo and hESC research in Australia are the Act on Prohibition of Human Cloning for Reproduction (2002), and the Act on Research Involving Human Embryos (2002), both being amended in December 2006 and effective from June 2007 on. They allow the creation of IVF and SCNT embryos as well as the derivation of hESC lines from these sources as well as research on hESC lines. PGD is allowed. Further regulatory changes are already expected in 2010.

In China the guidelines on human embryonic stem cell research from 2003, which were amended in March 2009, now allow the creation of supernumerary IVF and SCNT embryos for research. Moreover, PGD is permitted and the use of surplus PGD embryos and interspecies embryos are allowed.

Finland experienced the last amendment of the Medical Research Act 488 from 1999 in November 2009. The production of embryos for research purposes is prohibited. The legislative text is open to interpretation whether the creation of SCNT embryos is permitted or not, since the definition of an embryo refers to a “living group of cells resulting from fertilization”. The creation of an IVF embryo is not regulated in the law but the research on surplus IVF embryos is allowed. Regulation of the research on PGD embryos as well as the derivation of hESC lines from supernumerary PGD or IVF embryos is open to interpretation of the legislative text.

In India the DBT-ICMR guidelines regulate issues on stem cell research but have not become law yet. The creation of embryos by SCNT is allowed, this issue falls under “restricted areas of research” of the DBT-ICMR guidelines. The derivation of hESC lines from supernumerary IVF embryos is allowed, as is the research on embryos and hESC lines.

The Netherlands’ Embryo Act from 2002 was amended in 2007. The creation of embryos solely for research purposes is not allowed. The creation of IVF embryos for research purposes is not allowed. The derivation of hESC lines from supernumerary IVF and SCNT embryos for research is allowed if no other source than embryonic stem cells can be used as an alternative. PGD is allowed. Both, hESC line derivation and PGD must be applied at and approved by the CCMO (Central Committee for Research Involving Human Subjects). There are no further changes expected before 2012.

The Norwegian Biotechnology Act from 2007 was revised in 2008. It does not allow the creation of IVF embryos for research purposes. Research on supernumerary IVF embryos and PGD embryos is allowed. The derivation of hESC from supernumerary IVF embryos and SCNT for medical and biological research is allowed.

In Turkey the act “By-law on centers for in vitro fertilization and embryo transfer” concerning research on human embryos from 1987 was amended in 2005. IVF and PDG are legal in the country. hESC research is not regulated by a specific law. However, the Ministry of Health announced a 2005 memorandum stating that until specific guidelines are established, hESC derivation and research should not be performed in the country. Research with imported hESC lines may be performed. A new act is expected to be announced in 2010. For that, it is expected that hESC derivation for research purposes and hESC research will be regulated and allowed in certain qualified institutions and under certain conditions (such as lines with genetic diseases).

In the United Kingdom the Human Fertilisation and Embryology Act, which became law in 1990, was amended at the end of 2008 and legalizes the creation of embryos (including artificial techniques as SCNT) and the creation of interspecies embryos for research. The derivation of hESC lines from supernumerary IVF, SCNT and interspecies embryos are allowed. The definition of an embryo now includes embryos created by cloning and other processes.

In the USA there are different legal situations with respect to embryo and hESC research. The federal law concerning human embryo and embryonic stem cell (hESC) research is the Dickey-Wicker Amendment of 1995, which was again amended in 2009. The research on hESC lines and the derivation of hESC lines from IVF embryos, from embryos created by SCNT and from human admixed embryos is allowed but not for those projects with federal funding as outlined in the Dickey-Wicker Amendment. NIH-funded research is allowed with NIH-approved cell lines only. The NIH reviews information on informed consent and derivation for each line it registers. Non-federally funded research is reviewed by institutional review boards (IRB/SCRO). Creation of embryos for research must follow an IRB-approved protocol (45 CFR 46.107). In addition, IRB/SCRO committees tend to follow national guidelines such as those established by the National Academies of Science and the ISSCR.

Conclusion

Novel legislation and legislative changes need to take into account scientific progress and must be flexible enough to accommodate novel research results and the subsequent changes in the foundations of ethical views. It is unlikely that there will be a single universally accepted view on the ethical, legal, and moral status of the embryo as such, nor on the use of hESC lines derived thereof [5, 6]. But the recent advances in reprogramming show an enormous dynamic and developmental potential of almost any cell and thus question the basis for defining the embryo only as inherently totipotent. Totipotency is probably not inherent to cells derived from embryos and may become inducible by technical means from any differentiated adult cell, for example through the generation of sperm and oocytes from hiPSC. These questions are not yet or only partially reflected in legislative texts. Japan, for example, has prohibited the use of hiPSC for the creation of human gametes, embryos, and their implantation into animal or human wombs [9, 10]. It is therefore expected that the legislative and regulatory landscape will continue to change and that the pressure for international harmonization and transparency will increase.

An essential requirement is therefore the transparent information of what can be done with hiPSC and hESC. One of the tasks of the hESCreg is the reflection of international pluralism by providing information on each registered cell including its source and characteristics, as well as the ethical provenance [6, 7, 8]. This will be one aspect for safeguarding high standards in relation to ethical concerns and transparency in research. Consequently, the European Commission might use hESCreg as a central reference for all funding decisions on proposed hESC research projects within the Seventh EU Framework Programme.

Furthermore, hESCreg is also involved in providing information to the public about this highly sensitive field of research and its legal framework. By providing transparency an increased acceptance of this work is expected. Future tasks of the registry will include the establishment of a pluripotent stem cell registry at the international level, the inclusion of all types of pluripotent stem cells (hiPSC and others), the integration of a knowledge-service tool, the inclusion of banking service tools, the provision of an open and standardized common forum for exchange, and last but not least the development of guidelines for standards, governance, and ethical procurement of pluripotent stem cells.

References

1. Thomson, JA; Itskovitz-Eldor, J; Shapiro, SS; Waknitz, MA; Swiergiel, JJ; Marshall, VS; Jones, JM. Science. 1998 Nov 6; 282(5391):1145-7. Embryonic stem cell lines derived from human blastocysts. Science 1998 Dec 4; 282(5395):1827.

2. Rideout WM 3rd, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell. 2002 Apr 5; 109(1):17-27.

3. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663-76. Epub 2006 Aug 10.

4. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc. 2007;2(12):3081-9.

5. Cervera RP, Stojkovic M. Developments and Challenges in Human Embryonic Stem Cell Research in Spain. Stem Cell Rev Rep. 2009 Oct 3. [Epub ahead of print]

6. Elstner A, Damaschun A, Kurtz A, Stacey G, Arán B, Veiga A, Borstlap J. The changing landscape of European and international regulation on embryonic stem cell research. Stem Cell Res. 2009 Mar;2(2):101-7. Epub 2008 Nov 17.

7. Borstlap J, Stacey G, Kurtz A, Elstner A, Damaschun A, Arán B, Veiga A. First evaluation of the European hESCreg. Nat Biotechnol. 2008 Aug; 26(8):859-60.

8. Sipp, D., 2008. Q & A: Anna Veiga. Nat Med. 2008 Mar;14(3):234

9. Stocum, D.L. Zupanc G.K. Stretching the limits: Stem Cells in Regeneration Science. Dev Dyn. 2008 Dec; 237(12):3648-71. Review.

10. Cyranoski D. Stem cells: 5 things to know before jumping on the iPS bandwagon. Nature 452: 406-408; 2008.

Acknowledgements

The authors gratefully acknowledge the representatives of the National Contacts of the Human European Stem Cell Registry — hESCreg — for their contributions, input and helpful discussions. Especially we would like to thank Claus Yding Andersen, Necati Findikli, Derek Hei, Maneesha Inamdar, Anna Michalska, Christine Mummery, Timo Otonkoski, Glyn Stacey Benjamin Reubinoff, Arne Sunde and Fanyi Zeng. Many thanks to Luis Huegel for his assistance in layout work.

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["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13650" ["VALUE"]=> array(2) { ["TEXT"]=> string(340) "<p>Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга, <br>Йори Борстлап, Андреас Куртц</p><p>* Вклад обоих авторов одинаков</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(310) "

Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга,
Йори Борстлап, Андреас Куртц

* Вклад обоих авторов одинаков

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Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, www.hescreg.eu), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.

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Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

* Both authors contributed equally

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1Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Germany; 2The UK Stem Cell Bank, National Institute for Biological Standards and Control, South Mimms, UK; 3Banc de Linies Cel.lulars, Center of Regenerative Medicine Barcelona (CMRB); 4Institut Universitari Dexeus, Barcelona, Spain

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The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.

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Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

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Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

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The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.

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The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.

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1Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Germany; 2The UK Stem Cell Bank, National Institute for Biological Standards and Control, South Mimms, UK; 3Banc de Linies Cel.lulars, Center of Regenerative Medicine Barcelona (CMRB); 4Institut Universitari Dexeus, Barcelona, Spain

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1Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Germany; 2The UK Stem Cell Bank, National Institute for Biological Standards and Control, South Mimms, UK; 3Banc de Linies Cel.lulars, Center of Regenerative Medicine Barcelona (CMRB); 4Institut Universitari Dexeus, Barcelona, Spain

" } ["AUTHORS"]=> array(38) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(9) { [0]=> string(5) "13674" [1]=> string(5) "13675" [2]=> string(5) "13676" [3]=> string(5) "13677" [4]=> string(5) "13678" [5]=> string(5) "13679" [6]=> string(5) "13680" [7]=> string(5) "13681" [8]=> string(5) "13682" } ["VALUE"]=> array(9) { [0]=> string(3) "958" [1]=> string(3) "959" [2]=> string(3) "960" [3]=> string(3) "962" [4]=> string(3) "963" [5]=> string(3) "964" [6]=> string(3) "965" [7]=> string(3) "966" [8]=> string(3) "967" } ["DESCRIPTION"]=> array(9) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(9) { [0]=> string(3) "958" [1]=> string(3) "959" [2]=> string(3) "960" [3]=> string(3) "962" [4]=> string(3) "963" [5]=> string(3) "964" [6]=> string(3) "965" [7]=> string(3) "966" [8]=> string(3) "967" } ["~DESCRIPTION"]=> array(9) { [0]=> string(0) "" [1]=> string(0) "" [2]=> string(0) "" [3]=> string(0) "" [4]=> string(0) "" [5]=> string(0) "" [6]=> string(0) "" [7]=> string(0) "" [8]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> array(9) { [0]=> string(55) "Anja Elstner" [1]=> string(56) "Annette Noack" [2]=> string(62) "Alexander Damaschun" [3]=> string(54) "Glyn Stacey" [4]=> string(56) "Begoňa Arán" [5]=> string(58) "Ilona Gawronska" [6]=> string(53) "Anna Veiga" [7]=> string(57) "Joeri Borstlap" [8]=> string(56) "Andreas Kurtz" } ["LINK_ELEMENT_VALUE"]=> bool(false) } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13650" ["VALUE"]=> array(2) { ["TEXT"]=> string(340) "<p>Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга, <br>Йори Борстлап, Андреас Куртц</p><p>* Вклад обоих авторов одинаков</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(310) "

Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга,
Йори Борстлап, Андреас Куртц

* Вклад обоих авторов одинаков

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(310) "

Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга,
Йори Борстлап, Андреас Куртц

* Вклад обоих авторов одинаков

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["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13613" ["VALUE"]=> string(22) "12/30/2009 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "12/30/2009 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL ["DISPLAY_VALUE"]=> string(32) "12/30/2009 12:00:00 am" } ["KEYWORDS"]=> array(38) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(4) { [0]=> string(5) "13670" [1]=> string(5) "13671" [2]=> string(5) "13672" [3]=> string(5) "13673" } ["VALUE"]=> array(4) { [0]=> string(3) "968" [1]=> string(3) "969" [2]=> string(3) 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string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13569" ["VALUE"]=> string(3) "958" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "958" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(55) "Anja Elstner" ["LINK_ELEMENT_VALUE"]=> bool(false) } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13651" ["VALUE"]=> array(2) { ["TEXT"]=> string(2890) "<p class="bodytext">Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, <a href="http://www.hescreg.eu/" target="_blank">www.hescreg.eu</a>), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2836) "

Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, www.hescreg.eu), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.

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Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, www.hescreg.eu), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.

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Introduction

Clinical gene therapy is a very ambitious intent. The general principle sounds as easy as it is ingenious. Instead of treating the symptoms of severe genetic diseases such as immunodeficiencies or metabolic disorders, gene therapy intends to cure the underlying genetic defect by introducing a corrected copy of the mutated gene, or even by correcting the affected gene itself. In the context of disorders affecting the hematopoietic system, patient-derived cells can be treated ex vivo with engineered gene vectors designed to deliver the therapeutic gene. Except in those diseases associated with a strong selective advantage of the gene-modified cells, a preparatory “conditioning” by cytoreductive treatment may be required to promote engraftment.

Stable gene transfer, and therefore long-term genetic modification, is achieved by gene vectors, which integrate their genetic material and the therapeutic gene respectively into the chromatin of the target cells. Unlike classical pharmaceutical drug treatment, gene therapy is an approach highly specific to the patient and the disease. Parameters like cell source and origin, vector type, therapeutic dose, route of administration and, in particular, the transgene itself have to be adapted to each specific approach and medicinal purpose. For example, between 1989 and 2009 there were 1537 clinical gene therapy trials approved employing 35 different vector types (predominantly derived from Adenovirus, Retrovirus or naked DNA) in more than 8 different fields of medicine (predominantly cancer) (http://www.wiley.co.uk/genetherapy/clinical/). The consequence of the diversity of the products is a challenge for legal regulation, which should normally be universally valid while giving specific guidance to certain therapies in order to guarantee the safety and efficacy of the individual products.

While a gene therapy approach allows for the desired efficient long-term correction of a genetic defect on the one hand, it also brings up the concern of side effects on the other. The most noted example has been the clinical gene therapy trial for treatment of the rare genetic disorder X-linked severe combined immunodeficiency (X-SCID). While the majority of treated patients benefited from a life-saving and long-term immune reconstitution, the occurrence of lymphoproliferative disease due to insertional mutagenesis in 5 patients to date has gained notoriety [1, 2]. Integration site analysis revealed vector integrations close to cellular proto-oncogenes such as the LMO2 gene, known to be activated by chromosomal translocations in T-lymphoblastic leukemia [3, 4]. These severe adverse events made the theoretical concerns a reality. Additional concerns related to immunogenicity, spread of genetic sequences or toxic and infectious byproducts of vector preparations cause many gene therapy products to be classified as high-risk products that need to be strongly regulated by the authorities. This poses a tremendous challenge, since regulation can only be defined in general terms and an all-in-one document suitable for every purpose and individual need of a product cannot be established. To overcome this dilemma, case-by-case considerations are indicated.

Since researchers who invent the individual product initiate many clinical gene therapy trials, this review targets those investigators planning to enter the clinical development phase and initiating a clinical trial. It will clarify the complex situation and will give an overview of the current regulatory status as well as important points to consider before applying for a clinical trial authorization. This review involves preclinical and clinical issues as well as references to the necessary documents to be prepared.

Viral gene transfer and its associated risks

The regulatory framework should define uniform requirements in order to ensure compliance with quality standards and therefore guarantee the safety and well being of trial participants. In consideration of the major risks accompanied by viral gene transfer, it becomes clear that a thorough and complex regulatory framework is needed to control these biological products. As indicated above, the complexity of the individual product itself accounts for the necessity for evaluation of the risks and benefits of a certain gene therapy application on a case-by-case basis.

Integrating replication-defective vectors based on gamma-retroviruses have been frequently used in initial gene therapy protocols, and their risks will therefore be discussed as an example. Target cells are transduced in most cases ex vivo with the viral vector preparation. Shortly after entry of the retroviral particles, the viral RNA carrying the transgene of choice is reverse-transcribed into dsDNA, and a preintegration complex (PIC) is formed in which the DNA is associated with retroviral and cellular proteins (Figure 1). After translocation to the nucleus, the retroviral DNA including the transgene is stably integrated into the chromosomal DNA by the viral protein integrase.

Figure 1. The retroviral life cycle (reproduced with permission from the Journal Molecular Therapy (Nature Publishing Group); adapted from [5])

2009-4-en-Voelkel-et-al-Figure-1_01.JPG


The integration of the transgene makes the desired correction of the genetic defect possible in the first place, not only in the transduced cell but also in its progeny. However, at the same time it forms the basis of one of the major safety concerns of integrating retroviral vectors: insertional mutagenesis. The process of integration is highly efficient but occurs in a semi-random manner with respect to the targeted genetic loci. Although gamma-retroviral integration tends to occur preferentially in open chromatin regions, which is associated with actively transcribed genes [6], it does not favor a specific target sequence. Therefore, insertion of the transgene in a non-predictable unspecific way may lead to activation, inactivation or truncation of cellular genes adjacent to the site of integration. Cellular proto-oncogenes might be placed under control of the viral enhancer/promoter elements resulting in a non-physiological expression of the respective gene with loss of cellular regulation. The tumorigenic risk associated with such an event appears to be highly context dependent. Available evidence suggests that additional mutations are required before cells transform to overt malignancy [7].

The concern of genotoxicity especially affects the first generation of retroviral-based gene transfer vectors in which the transgene is driven by the strong long terminal repeat (LTR) enhancer/promoter elements of the virus. New strategies in vector design with reduced potential for enhancer-mediated interaction with adjacent cellular genes may decrease the risk of genotoxicity, e.g., the use of self-inactivating (SIN) vectors [8], the incorporation of cellular promoters [9], the use of chromatin insulators [10], or the use of lentivirus-based vectors, which have a lower likelihood of integration in promoter-proximal or other regulatory gene regions [11]. In all circumstances, the genotoxic potential of a given vector designed for clinical use needs to be preclinically assessed and evaluated.

Another concern regarding the risk of oncogenesis is the formation of replication-competent retrovirus (RCR). Although retroviral vectors are replication-deficient due to the lack of the sequences encoding for the structural and enzymatic viral proteins, there is still the possibility of formation of RCR by recombination of the vector sequence with the so-called “helper” plasmids or with other, endogenous retroviral genetic information present in the producer or target cells [12]. As a consequence, unintended infection of target or even off-target cells might occur. This might introduce harmful viral pathogens into treated patients.

In order to assess the risk of RCR formation, investigators should evaluate the presence of homologous sequences suitable for recombination in the vector constructs, as well as the presence of endogenous viruses in the packaging cells. If possible, such sequences should be avoided or at least limited. Nevertheless, strict testing for the presence of RCR in retroviral vector batches intended for clinical application is required.

Another major concern of viral gene transfer is vertical germ line transmission. In general, gene therapy trials with the aim of direct germ line manipulation are prohibited [28]. Nevertheless, also in somatic gene therapy the concern of inadvertent germ line integration exists and gained new attention when semen of clinical trial participants for treatment of hemophilia tested positive for vector sequences [13, 14]. Although this does not necessarily imply that vector sequences were present in germ cells, this observation underlines the need for diligent biodistribution studies. The risk of germline transmission is in particular dependent on the biodistribution pattern of a given vector. In this regard, the route of administration, vector type and dose, and the innate and adapted immunity of the patient play pivotal roles. A replication deficient integrating vector used for ex vivo transduction of the target cell might have a much lower risk than the same vector applied systemically in an in vivo application. At the same time, a gamma-retroviral vector which can only transduce dividing cells might have a lower risk in transducing mature sperm cells than a lentiviral vector, which has the ability to also infect non-dividing cells. Still, spermatogonial stem cells that have a high proliferation activity might be accessible for gamma-retroviral vectors. Therefore, regulatory agencies have developed guidelines describing how to address the risk of inadvertent germ line transmission in preclinical studies (see below and Table 1).

Table 1. Applicable guidelines addressing GTMPs

2009-4-en-Voelkel-et-al-Tab01.JPG

Regulatory framework for Gene Therapy Medicinal Products

Currently, the regulatory situation for Gene Therapy Medicinal Products (GTMPs) is evolving rapidly on the European level. The new core regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products (ATMPs), which became effective in December 2008 (from here on referred to as ‘ATMP regulation’), lays the foundation for a harmonized regulatory situation applicable for all member states in the European Communion. According to Article 2 of this regulation, GTMPs together with Somatic Cell Therapy Medicinal Products and Tissue Engineered Products are classified as ATMPs (Figure 2). Until incorporation of this regulation, these products fell in a regulatory gap somewhere in between legislation 93/42/EEC on Medical Devices and Directive 2001/83/EC on Medicinal Products. The new ‘ATMP regulation’ fills this gap and "lays down specific rules concerning the authorization, supervision and pharmacovigilance of Advanced Therapy Medicinal Products” [50, Article 1].

2009-4-en-Voelkel-et-al-Figure-2.JPG

For the definition of a GTMP itself, the regulation refers to Annex I Part IV of Directive 2001/83/EC, as amended by Directive 2003/63/EC, which states: “For the purposes of this Annex, Gene Therapy Medicinal Product shall mean a product obtained through a set of manufacturing processes aimed at the transfer, to be performed either in vivo or ex vivo, of a prophylactic, diagnostic or therapeutic gene (i.e. a piece of nucleic acid), to human/animal cells and its subsequent expression in vivo.” Within the implementation of the ‘ATMP regulation’, this annex is currently under revision in order to adjust it to the specific characteristics of ATMPs (Figure 2). There is no draft version currently available, but the outcome of the public consultation paper as well as single contributions can be found on the webpage of the European Commission.

On the national German level, GTMPs are similarly defined as Medicinal Products in the Medicinal Products Act (“AMG”), Section 4 No. 9, [48]. Within the 15th amendment of the Medicinal Products Act, the new ATMP regulation will be implemented into national German law. Though a regulation, the translation into national law is necessary because the ‘ATMP regulation’ amends Directive 2001/83/EC.

GTMPs are often very complex products that may contain other components that are regulated by additional legislation. The GTMP may for instance contain human cells or tissues. Regarding the quality and safety for the donation, procurement and testing of these cells or tissues, Directive 2004/23/EC as implemented by Directive 2006/17/EC applies (Figure 3A). Directive 2004/23/EC is already transposed into national law by the German Tissue Act (“Gewebegesetz”). The processing, preservation, storage and distribution of these cells and tissues, however, fall under Section 14 of the ‘ATMP regulation’. When the GTMP also contains human blood or blood components, Directive 2002/98/EC as implemented by Directives 2004/33/EC, 2005/61/EC and 2005/62/EC applies (Figure 3B). On the German level, these aspects are addressed in the Medicinal Products Act and Transfusion Law.

In addition, the GTMP may be a combination product consistent of a Medicinal Product and Medical Device. This would, for instance, be the case if the gene-modified cells are applied to the patient via a specific biodelivery implant. Whether the regulatory rules and standards of Medicinal Products or of Medical Devices apply to combination products generally depends on their mode of action. Nevertheless, if ATMPs (and therefore GTMPs) are incorporated into a combination product, the ‘ATMP regulation’ applies regardless of the function of the Medical Device [50, Section 4]. However, the latter have to furthermore fulfill the quality and safety requirements of Directive 93/42/EEC (in case of a Medical Device) and accordingly Directive 90/385/EEC (in case of an active implantable Medical Device) as amended by Directive 2007/47/EC (Figure 3C). On the German level, both directives are implemented by the German Act on Medical Devices (“MPG”).

For clinical trials involving GTMPs, the overall requirements and ethical standards of the Clinical Trial Directive 2001/20/EC apply as well as for all other medicinal products (Figure 3D). In Germany, this directive is translated into national law by the GCP Ordinance (“GCP-Verordnung”). Furthermore, the German Medicinal Products Act applies, in particular concerning clinical trials in Chapter 6, together with the general considerations for clinical trials laid down in ICH E8 Step 5 [27]. Within the scope of the implementation of the ‘ATMP regulation’, the standards of good clinical practices shall be expanded to the specific needs of ATMPs [50, Article 4]. The adaption process is currently proceeding. A public consultation paper is already published on the European Commission webpage. The public consultation process has been closed so that a draft document on good clinical practice specific for ATMPs is expected to be published soon.

In Germany, the competent authority concerning clinical trial authorization related to GTMPs is the Paul-Ehrlich-Institute (PEI). General principles for requesting the authorization of a clinical trial in Germany are laid down in the third Notification of the joint announcement from PEI and the Federal Institute for Drugs and Medical Devices (BfArM) (third Notification).

In Germany there are some particularities for GTMPs compared to conventional medicinal products. While for example the ethics committee has to give an opinion within 60 days after a clinical trial application (multicentric trial) for conventional medicinal products, the time period extends up to 180 days if GTMPs are concerned [44, Section 8(4)]. Furthermore, the competent authority has to provide a written approval (explicit authorization) for clinical trials concerning GTMPs within 90 days after complete clinical trial application. This period may be extended to 180 days if the authority consults experts or professional opinions for decision-making [44, Section 9(4)].

The manufacture of GTMPs needs to be consistent with the requirements of Directive 2003/94/EC on Good Manufacturing Practice (“GMP“) (Figure 3E). Due to the complexity of ATMPs (and GTMPs) and the extensive manufacturing processes, the ‘ATMP regulation’ implicates an adaption of the guidelines for GMP to the specific situation of ATMPs [50, Article 5].

Figure 3. Regulatory framework for Gene Therapy Medicinal Products

2009-4-en-Voelkel-et-al-Figure-3.JPG

Currently, a draft version of the adapted Eudralex Volume 4 Annex 2 on the manufacture of biological medicinal products is published. Furthermore, the European Pharmacopoeia serves as a legally binding framework for quality standards of medicinal products in Europe [43]. The General Chapter 5.14, which deals with GTMPs, gives instructions for the testing of batches of recombinant vectors and gene-modified cells. In Germany, good manufacturing practice is regulated in the ordinance for the manufacture of medicinal products and active pharmaceutical ingredients (AMWHV).

There are in addition various guidelines published addressing manufacturing and quality aspects during the development of ATMPs (Table 1). One is the multidisciplinary “Guideline on human Cell-Based Medicinal Products” of the European Medicines Agency (EMEA) [35], which gives advice for the “development, manufacturing and quality control as well as non-clinical and clinical development of Cell-Based Medicinal Products” which also include GTMPs. The guideline is aimed at products already in the phase of marketing authorization but the general considerations also apply for clinical trials. The EMEA “Note for guidance on the quality, preclinical and clinical aspects of Gene Transfer Medicinal Products” [25] gives recommendations for producing data aiming at an application for marketing authorization. Affiliated is the “Concept paper on the development of a guideline on the quality, preclinical and clinical aspects of medicinal products containing genetically modified cells” by EMEA [40]. If the GTMP was generated with the help of lentiviral vectors, the EMEA “Guideline on development and manufacture of lentiviral vectors” gives advice regarding quality and safety of the vectors [24].

Importantly, the specific safety aspects related to GTMPs have to be considered and analyzed before the products can be used in the clinic. The EMEA “Guideline on the non-clinical studies required before first clinical use of Gene Therapy Medicinal Products” [38] specifies which studies are essential prior to the first application to humans. This includes but is not limited to non-clinical proof of concept studies, biodistribution studies, as well as studies on dose finding, germ line transmission, immunotoxicity and studies addressing the environmental risks/shedding. Specific recommendations for the later are defined in the EMEA “Guideline on scientific requirements for the environmental risk assessment of Gene Therapy Medicinal Products” [39]. This guideline states: "Generally the purpose of clinical trials are to study the adsorption, distribution, metabolism and excretion of one or more Investigational Medicinal Products with the object of ascertaining its (their) safety and/or efficacy ([28]; definition of a clinical trial). As such the evaluation of vector shedding is a requirement for a phase I study.” Data of clinical trials regarding environmental risks need to be collected and integrated in a full environmental risk assessment (ERA) needed for a marketing authorization procedure. Other guidelines dealing with environmental risk assessments of genetically modified organisms are EMEA/BWP/473191/06-corr and EMEA/CHMP/BWP/135148/04.

Furthermore, in terms of studies addressing the risk and ethical concerns of inadvertent germline transmission, separate guidelines are available. The EMEA “Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors” [34] recommends adjusted study designs depending on the type of vector used, as well as providing a decision tree regarding the necessary questions to be addressed by biodistribution and germ line transmission studies. Also a considerations paper of the International Conference On Harmonization Of Technical Requirements For Registration Of Pharmaceuticals For Human Use (ICH) is available on this topic and can be consulted in this regard (ICH considerations, general principles to address the risk of inadvertent germline integration of gene therapy vectors). The ICH S2B document “Note for guidance on genotoxicity” [26], however, gives recommendations for studies to address the risk of genotoxicity and can give advice in these questions.

If patients have been treated with a gene therapy approach in a clinical trial, clinical monitoring as well as intensive follow-up care should be performed in order to detect adverse events at an early stage to avoid clinical implications and to collect safety data. The “Guideline on follow-up of patients administered with Gene Therapy Medicinal Products” [41] gives recommendations in this regard.

Regulation (EC) No 726/2004 already regulates the marketing authorization procedure of biotechnology medicinal products on the European level. In this context, the products pass through a centralized authorization procedure at the EMEA in order to assess their quality, safety and efficacy. The technical requirements needed to prove the latter are defined in Annex I to Directive 2001/83/EC.

Nevertheless, the complexity and variety of ATMPs may result in a situation of very specific and individual questions to be addressed. Within the scope of the ‘ATMP regulation’, the Committee for Advanced Therapies (CAT) will be established within the EMEA in order to provide strong expertise in this field and exhibit draft opinions on ATMP applications presented to EMEA [50, Chapter 7]. Therefore, Regulation (EC) No 726/2004 needs to be amended. Currently, the CAT is in the process of establishment within the EMEA. Updated details can be found on the respective webpage of EMEA. Within the context of a marketing authorization, the standards for pharmacovigilance described in Regulation 726/2004 apply. Since clinical trials are typically powered for efficacy and furthermore the duration of the respective trials might not allow the detection of long term adverse events, the application has to provide a plan to ensure the follow-up of adverse reactions after marketing authorization. A specific EMEA guideline giving further recommendations on “Safety and Efficacy Follow-Up – Risk management of Advanced Therapy Medicinal Products” is already published [33]. Another measure of safety is the full traceability of the product (including the starting materials) and the treated patient. According to the ‘ATMP regulation’, the marketing authorization holder for an ATMP is responsible for setting up a traceability system [50, Article 15]. If human tissues or cells are involved, the traceability standards defined in Directive 2004/23/EC also apply, as do the requirements of Directive 2002/98/EC concerning human blood and blood components, respectively.

Finally, it should be noted that both the European agency EMEA and the German agency PEI (in charge of ATMPs) provide scientific advice. Investigators are welcome to consult the agencies in all phases of project development in order to obtain important project-specific advice, e.g., before applying for a clinical trial or marketing authorization. Details can be found on the webpages of EMEA or PEI, respectively.

Outlook

Application of new technologies of gene therapy to the treatment of diseases will yield the greatest benefits if approached on a sound scientific and medical basis. Regulatory guidelines are the basis of (i) current scientific knowledge, (ii) scientific expertise in a given research area, and (iii) the result of a continuous interaction between researchers and regulatory experts. Gene therapy has entered the stage of clinical evaluation. As always at the frontier of bench to bedside research, patient safety must be the first and foremost consideration in human gene therapy before one enters the stage of extensive clinical trials to assess efficacy.

References

Index of scientific references

1. Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118(9):3132-3142.

2. Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118(9):3143-50.

3. Boehm T, Foroni L, Kaneko Y, et al. The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc. Natl. Acad. Sci. 1991;88:4367–4371.

4. Royer-Pokora B, Loos U, and Ludwig WD. TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukemia with the t(11;14)(p13;q11). Oncogene. 1991;6:1887–1893.

5. Baum C, Schambach A, Bohne J, and Galla M. Retrovirus Vectors: Toward the Plentivirus? Mol Ther. 2006;13:1050-1063.

6. Wu X, Li Y, Crise B, and Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science. 2003;300(5626):1749-1751.

7. Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446:758-764.

8. Modlich U, Bohne J, Schmidt M, et al. Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood. 2006;108:2545-2553.

9. Zychlinski D, Schambach A, Modlich U, et al. Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors. Mol Ther. 2008;16(4):718-725.

10. Emery DW, Yannaki E, Tubb J, et al. Development of virus vectors for gene therapy of beta chain hemoglobinopathies: flanking with a chromatin insulator reduces gamma-globin gene silencing in vivo. Blood. 2002;100:2012-2019.

11. De Palma M, Montini E, Santoni de Sio FR, et al. Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells. Blood.2005;105(6):2307-15.

12. Chong H, Starkey W, and Vile RG. A replication-competent retrovirus arising from a split-function packaging cell line was generated by recombination events between the vector, one of the packaging constructs, and endogenous retroviral sequences. J Virol.1998;72:2663–2670.

13. Marshall E. Gene therapy. Viral vectors still pack surprises. Science. 2001;294(5547):1640.

14. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342-7.


Index of regulatory references

15. 3. Notification (“3. Bekanntmachung”) of the Federal Institute for Drugs and Medical Devices and the Paul Ehrlich Institute of 10 August 2006 on the clinical trial of medicinal products for human use.

16. Commission Directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use. OJ L 159, 27.06.2006, p.46.

17. Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use.OJ L 262, 14.10.2003, p.22.

18. Commission Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components. OJ L 91, 30.03.2004, p.25.

19. Commission Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards traceability requirements and notification of serious adverse reactions and events. OJ L 256, 01.10.2005, p.32.

20. Commission Directive 2005/62/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications relating to a quality system for blood establishments. OJ L 256, 01.10.2005, p.41.

21. Commission Directive 2006/17/EC of 8 February 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells. OJ L 38, 09.02.2006, p.40.

22. Council Directive 90/385/EEC  of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices. OJ L 189, 20.07.1990, p.17

23. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. OJ L 169, 12.07.1993, p.1.

24. CHMP/BWP/2458/03 of the Committee for Medicinal Products for Human Use (CHMP) of 26 May 2005. Guideline on development and manufacture of lentiviral vectors.

25. CPMP/BWP/3088/99 of the Committee for Proprietary Medicinal Products (CPMP) of 24 April 2001. Note for Guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products.

26. CPMP/ICH/174/95 ICH Topic S 2 B of March 1998. Genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals, Step 5. Note for guidance on genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals.

27. CPMP/ICH/291/95 ICH Topic E 8 of March 1998. General considerations for clinical trials, step 5. Note for guidance on general considerations for clinical trials.

28. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJ L 121, 1.5.2001, p.34.

29. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. OJ L 311, 28.11.2001, p.67.

30. Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood componentsand amending Directive 2001/83/EC. OJ L 33, 08.02.2003, p.30.

31. Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. OJ L 102, 07.04.2004, p.48.

32. Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market.

33. EMEA/149995/08 of the Committee for Medicinal Products for Human Use (CHMP) of 20 November 2008. Guideline on safety and efficacy follow-up – risk management of advanced therapy medicinal products.

34. EMEA/273974/05 of the Committee for Medicinal Products for Human Use (CHMP) of 16 November 2006. Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors.

35. EMEA/CHMP/410869/06 of the Committee for Medicinal Products for Human Use (CHMP) of 21 May 2008. Guideline on human cell-based medicinal products.

36. EMEA/CHMP/BWP/135148/04 of the Committee for Medicinal Products for Human Use (CHMP) of 20 January 2005. Environmental risk assessments for medicinal products containing, or consisting of, genetically modified organisms (GMOs) (Module 1.6.2).

37. EMEA/CHMP/BWP/473191/06 - Corr of the Committee for Medicinal Products for Human Use (CHMP) of 11 December 2006. Guideline on environmental risk assessments for medicinal products consisting of, or containing, genetically modified organisms (GMOs).

38. EMEA/CHMP/GTWP/125459/06 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Guideline on the non-clinical studies required before first clinical use of gene therapy medicinal products.

39. EMEA/CHMP/GTWP/125491/06 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Guideline on scientific requirements for the environmental risk assessment of gene therapy medicinal products.

40. EMEA/CHMP/GTWP/405681/06 of the Committee for Medicinal Products for Human Use (CHMP) of 24 May 2007. Concept paper on the development of a guideline on the quality, preclinical and clinical aspects of medicinal products containing genetically modified cells.

41. EMEA/CHMP/GTWP/60436/07 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Draft guideline on follow-up of patients administered with gene therapy medicinal products.

42. Eudralex Volume 4. Good manufacturing practice guidelines. Volume 4 of “The rules governing medicinal products in the European Union”. http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol4_en.htm

43. European Pharacopoeia. http://www.pheur.org

44. GCP Ordinance (“GCP-Verordnung“). Of the German Federal Ministry for Health and Social Security of 09 August 2004 for good clinical practice in the conduct of clinical trials on medicinal products for human use. Federal Law Gazette I, 12.08.2004, p.2081.

45. German Act on Medical Devices (“Medizinproduktegesetz”) of the Federal Republic of Germany of 02.08.1994 in the version of the notification of the Law of 07.08. 2002. Federal Law Gazette I p.3146.

46. German Tissue Act (“Gewebegesetz“) of the German Federal Parliament of 20 July 2007 on the quality and safety of human tissues and cells. Federal Law Gazette I, 27.07.2007, p.1574.

47. ICH Considerations of the International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use of 25 October 2006. General principles to address the risk of inadvertent germline integration of gene therapy vectors.

48. Medicinal Products Act (“Arzneimittelgesetz”) of the Federal Republic of Germany of 24.08.1976 in the version of the notification of the Law of 12th December 2005. Federal Law Gazette I p.3394.

49. Ordinance for the manufacture of medicinal products and active pharmaceutical ingredients (“AMWHV”) of the German Federal Ministries for Health and Food, Agriculture and Consumer Protection of 03 November 2006. Federal Law Gazette I, 09.11.2006, p.2523.

50. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. OJ L 324, 10.12.2007, p.121.

51. Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. OJ L 136, 30.04.2004, p.1.

52. Transfusion Law (“Transfusionsgesetz”) of the Federal Republic of Germany of 01.07.1998 in the version of the notification of the Law of 28.08.2007. Federal Law Gazette I p.2169.

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Introduction

Clinical gene therapy is a very ambitious intent. The general principle sounds as easy as it is ingenious. Instead of treating the symptoms of severe genetic diseases such as immunodeficiencies or metabolic disorders, gene therapy intends to cure the underlying genetic defect by introducing a corrected copy of the mutated gene, or even by correcting the affected gene itself. In the context of disorders affecting the hematopoietic system, patient-derived cells can be treated ex vivo with engineered gene vectors designed to deliver the therapeutic gene. Except in those diseases associated with a strong selective advantage of the gene-modified cells, a preparatory “conditioning” by cytoreductive treatment may be required to promote engraftment.

Stable gene transfer, and therefore long-term genetic modification, is achieved by gene vectors, which integrate their genetic material and the therapeutic gene respectively into the chromatin of the target cells. Unlike classical pharmaceutical drug treatment, gene therapy is an approach highly specific to the patient and the disease. Parameters like cell source and origin, vector type, therapeutic dose, route of administration and, in particular, the transgene itself have to be adapted to each specific approach and medicinal purpose. For example, between 1989 and 2009 there were 1537 clinical gene therapy trials approved employing 35 different vector types (predominantly derived from Adenovirus, Retrovirus or naked DNA) in more than 8 different fields of medicine (predominantly cancer) (http://www.wiley.co.uk/genetherapy/clinical/). The consequence of the diversity of the products is a challenge for legal regulation, which should normally be universally valid while giving specific guidance to certain therapies in order to guarantee the safety and efficacy of the individual products.

While a gene therapy approach allows for the desired efficient long-term correction of a genetic defect on the one hand, it also brings up the concern of side effects on the other. The most noted example has been the clinical gene therapy trial for treatment of the rare genetic disorder X-linked severe combined immunodeficiency (X-SCID). While the majority of treated patients benefited from a life-saving and long-term immune reconstitution, the occurrence of lymphoproliferative disease due to insertional mutagenesis in 5 patients to date has gained notoriety [1, 2]. Integration site analysis revealed vector integrations close to cellular proto-oncogenes such as the LMO2 gene, known to be activated by chromosomal translocations in T-lymphoblastic leukemia [3, 4]. These severe adverse events made the theoretical concerns a reality. Additional concerns related to immunogenicity, spread of genetic sequences or toxic and infectious byproducts of vector preparations cause many gene therapy products to be classified as high-risk products that need to be strongly regulated by the authorities. This poses a tremendous challenge, since regulation can only be defined in general terms and an all-in-one document suitable for every purpose and individual need of a product cannot be established. To overcome this dilemma, case-by-case considerations are indicated.

Since researchers who invent the individual product initiate many clinical gene therapy trials, this review targets those investigators planning to enter the clinical development phase and initiating a clinical trial. It will clarify the complex situation and will give an overview of the current regulatory status as well as important points to consider before applying for a clinical trial authorization. This review involves preclinical and clinical issues as well as references to the necessary documents to be prepared.

Viral gene transfer and its associated risks

The regulatory framework should define uniform requirements in order to ensure compliance with quality standards and therefore guarantee the safety and well being of trial participants. In consideration of the major risks accompanied by viral gene transfer, it becomes clear that a thorough and complex regulatory framework is needed to control these biological products. As indicated above, the complexity of the individual product itself accounts for the necessity for evaluation of the risks and benefits of a certain gene therapy application on a case-by-case basis.

Integrating replication-defective vectors based on gamma-retroviruses have been frequently used in initial gene therapy protocols, and their risks will therefore be discussed as an example. Target cells are transduced in most cases ex vivo with the viral vector preparation. Shortly after entry of the retroviral particles, the viral RNA carrying the transgene of choice is reverse-transcribed into dsDNA, and a preintegration complex (PIC) is formed in which the DNA is associated with retroviral and cellular proteins (Figure 1). After translocation to the nucleus, the retroviral DNA including the transgene is stably integrated into the chromosomal DNA by the viral protein integrase.

Figure 1. The retroviral life cycle (reproduced with permission from the Journal Molecular Therapy (Nature Publishing Group); adapted from [5])

2009-4-en-Voelkel-et-al-Figure-1_01.JPG


The integration of the transgene makes the desired correction of the genetic defect possible in the first place, not only in the transduced cell but also in its progeny. However, at the same time it forms the basis of one of the major safety concerns of integrating retroviral vectors: insertional mutagenesis. The process of integration is highly efficient but occurs in a semi-random manner with respect to the targeted genetic loci. Although gamma-retroviral integration tends to occur preferentially in open chromatin regions, which is associated with actively transcribed genes [6], it does not favor a specific target sequence. Therefore, insertion of the transgene in a non-predictable unspecific way may lead to activation, inactivation or truncation of cellular genes adjacent to the site of integration. Cellular proto-oncogenes might be placed under control of the viral enhancer/promoter elements resulting in a non-physiological expression of the respective gene with loss of cellular regulation. The tumorigenic risk associated with such an event appears to be highly context dependent. Available evidence suggests that additional mutations are required before cells transform to overt malignancy [7].

The concern of genotoxicity especially affects the first generation of retroviral-based gene transfer vectors in which the transgene is driven by the strong long terminal repeat (LTR) enhancer/promoter elements of the virus. New strategies in vector design with reduced potential for enhancer-mediated interaction with adjacent cellular genes may decrease the risk of genotoxicity, e.g., the use of self-inactivating (SIN) vectors [8], the incorporation of cellular promoters [9], the use of chromatin insulators [10], or the use of lentivirus-based vectors, which have a lower likelihood of integration in promoter-proximal or other regulatory gene regions [11]. In all circumstances, the genotoxic potential of a given vector designed for clinical use needs to be preclinically assessed and evaluated.

Another concern regarding the risk of oncogenesis is the formation of replication-competent retrovirus (RCR). Although retroviral vectors are replication-deficient due to the lack of the sequences encoding for the structural and enzymatic viral proteins, there is still the possibility of formation of RCR by recombination of the vector sequence with the so-called “helper” plasmids or with other, endogenous retroviral genetic information present in the producer or target cells [12]. As a consequence, unintended infection of target or even off-target cells might occur. This might introduce harmful viral pathogens into treated patients.

In order to assess the risk of RCR formation, investigators should evaluate the presence of homologous sequences suitable for recombination in the vector constructs, as well as the presence of endogenous viruses in the packaging cells. If possible, such sequences should be avoided or at least limited. Nevertheless, strict testing for the presence of RCR in retroviral vector batches intended for clinical application is required.

Another major concern of viral gene transfer is vertical germ line transmission. In general, gene therapy trials with the aim of direct germ line manipulation are prohibited [28]. Nevertheless, also in somatic gene therapy the concern of inadvertent germ line integration exists and gained new attention when semen of clinical trial participants for treatment of hemophilia tested positive for vector sequences [13, 14]. Although this does not necessarily imply that vector sequences were present in germ cells, this observation underlines the need for diligent biodistribution studies. The risk of germline transmission is in particular dependent on the biodistribution pattern of a given vector. In this regard, the route of administration, vector type and dose, and the innate and adapted immunity of the patient play pivotal roles. A replication deficient integrating vector used for ex vivo transduction of the target cell might have a much lower risk than the same vector applied systemically in an in vivo application. At the same time, a gamma-retroviral vector which can only transduce dividing cells might have a lower risk in transducing mature sperm cells than a lentiviral vector, which has the ability to also infect non-dividing cells. Still, spermatogonial stem cells that have a high proliferation activity might be accessible for gamma-retroviral vectors. Therefore, regulatory agencies have developed guidelines describing how to address the risk of inadvertent germ line transmission in preclinical studies (see below and Table 1).

Table 1. Applicable guidelines addressing GTMPs

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Regulatory framework for Gene Therapy Medicinal Products

Currently, the regulatory situation for Gene Therapy Medicinal Products (GTMPs) is evolving rapidly on the European level. The new core regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products (ATMPs), which became effective in December 2008 (from here on referred to as ‘ATMP regulation’), lays the foundation for a harmonized regulatory situation applicable for all member states in the European Communion. According to Article 2 of this regulation, GTMPs together with Somatic Cell Therapy Medicinal Products and Tissue Engineered Products are classified as ATMPs (Figure 2). Until incorporation of this regulation, these products fell in a regulatory gap somewhere in between legislation 93/42/EEC on Medical Devices and Directive 2001/83/EC on Medicinal Products. The new ‘ATMP regulation’ fills this gap and "lays down specific rules concerning the authorization, supervision and pharmacovigilance of Advanced Therapy Medicinal Products” [50, Article 1].

2009-4-en-Voelkel-et-al-Figure-2.JPG

For the definition of a GTMP itself, the regulation refers to Annex I Part IV of Directive 2001/83/EC, as amended by Directive 2003/63/EC, which states: “For the purposes of this Annex, Gene Therapy Medicinal Product shall mean a product obtained through a set of manufacturing processes aimed at the transfer, to be performed either in vivo or ex vivo, of a prophylactic, diagnostic or therapeutic gene (i.e. a piece of nucleic acid), to human/animal cells and its subsequent expression in vivo.” Within the implementation of the ‘ATMP regulation’, this annex is currently under revision in order to adjust it to the specific characteristics of ATMPs (Figure 2). There is no draft version currently available, but the outcome of the public consultation paper as well as single contributions can be found on the webpage of the European Commission.

On the national German level, GTMPs are similarly defined as Medicinal Products in the Medicinal Products Act (“AMG”), Section 4 No. 9, [48]. Within the 15th amendment of the Medicinal Products Act, the new ATMP regulation will be implemented into national German law. Though a regulation, the translation into national law is necessary because the ‘ATMP regulation’ amends Directive 2001/83/EC.

GTMPs are often very complex products that may contain other components that are regulated by additional legislation. The GTMP may for instance contain human cells or tissues. Regarding the quality and safety for the donation, procurement and testing of these cells or tissues, Directive 2004/23/EC as implemented by Directive 2006/17/EC applies (Figure 3A). Directive 2004/23/EC is already transposed into national law by the German Tissue Act (“Gewebegesetz”). The processing, preservation, storage and distribution of these cells and tissues, however, fall under Section 14 of the ‘ATMP regulation’. When the GTMP also contains human blood or blood components, Directive 2002/98/EC as implemented by Directives 2004/33/EC, 2005/61/EC and 2005/62/EC applies (Figure 3B). On the German level, these aspects are addressed in the Medicinal Products Act and Transfusion Law.

In addition, the GTMP may be a combination product consistent of a Medicinal Product and Medical Device. This would, for instance, be the case if the gene-modified cells are applied to the patient via a specific biodelivery implant. Whether the regulatory rules and standards of Medicinal Products or of Medical Devices apply to combination products generally depends on their mode of action. Nevertheless, if ATMPs (and therefore GTMPs) are incorporated into a combination product, the ‘ATMP regulation’ applies regardless of the function of the Medical Device [50, Section 4]. However, the latter have to furthermore fulfill the quality and safety requirements of Directive 93/42/EEC (in case of a Medical Device) and accordingly Directive 90/385/EEC (in case of an active implantable Medical Device) as amended by Directive 2007/47/EC (Figure 3C). On the German level, both directives are implemented by the German Act on Medical Devices (“MPG”).

For clinical trials involving GTMPs, the overall requirements and ethical standards of the Clinical Trial Directive 2001/20/EC apply as well as for all other medicinal products (Figure 3D). In Germany, this directive is translated into national law by the GCP Ordinance (“GCP-Verordnung”). Furthermore, the German Medicinal Products Act applies, in particular concerning clinical trials in Chapter 6, together with the general considerations for clinical trials laid down in ICH E8 Step 5 [27]. Within the scope of the implementation of the ‘ATMP regulation’, the standards of good clinical practices shall be expanded to the specific needs of ATMPs [50, Article 4]. The adaption process is currently proceeding. A public consultation paper is already published on the European Commission webpage. The public consultation process has been closed so that a draft document on good clinical practice specific for ATMPs is expected to be published soon.

In Germany, the competent authority concerning clinical trial authorization related to GTMPs is the Paul-Ehrlich-Institute (PEI). General principles for requesting the authorization of a clinical trial in Germany are laid down in the third Notification of the joint announcement from PEI and the Federal Institute for Drugs and Medical Devices (BfArM) (third Notification).

In Germany there are some particularities for GTMPs compared to conventional medicinal products. While for example the ethics committee has to give an opinion within 60 days after a clinical trial application (multicentric trial) for conventional medicinal products, the time period extends up to 180 days if GTMPs are concerned [44, Section 8(4)]. Furthermore, the competent authority has to provide a written approval (explicit authorization) for clinical trials concerning GTMPs within 90 days after complete clinical trial application. This period may be extended to 180 days if the authority consults experts or professional opinions for decision-making [44, Section 9(4)].

The manufacture of GTMPs needs to be consistent with the requirements of Directive 2003/94/EC on Good Manufacturing Practice (“GMP“) (Figure 3E). Due to the complexity of ATMPs (and GTMPs) and the extensive manufacturing processes, the ‘ATMP regulation’ implicates an adaption of the guidelines for GMP to the specific situation of ATMPs [50, Article 5].

Figure 3. Regulatory framework for Gene Therapy Medicinal Products

2009-4-en-Voelkel-et-al-Figure-3.JPG

Currently, a draft version of the adapted Eudralex Volume 4 Annex 2 on the manufacture of biological medicinal products is published. Furthermore, the European Pharmacopoeia serves as a legally binding framework for quality standards of medicinal products in Europe [43]. The General Chapter 5.14, which deals with GTMPs, gives instructions for the testing of batches of recombinant vectors and gene-modified cells. In Germany, good manufacturing practice is regulated in the ordinance for the manufacture of medicinal products and active pharmaceutical ingredients (AMWHV).

There are in addition various guidelines published addressing manufacturing and quality aspects during the development of ATMPs (Table 1). One is the multidisciplinary “Guideline on human Cell-Based Medicinal Products” of the European Medicines Agency (EMEA) [35], which gives advice for the “development, manufacturing and quality control as well as non-clinical and clinical development of Cell-Based Medicinal Products” which also include GTMPs. The guideline is aimed at products already in the phase of marketing authorization but the general considerations also apply for clinical trials. The EMEA “Note for guidance on the quality, preclinical and clinical aspects of Gene Transfer Medicinal Products” [25] gives recommendations for producing data aiming at an application for marketing authorization. Affiliated is the “Concept paper on the development of a guideline on the quality, preclinical and clinical aspects of medicinal products containing genetically modified cells” by EMEA [40]. If the GTMP was generated with the help of lentiviral vectors, the EMEA “Guideline on development and manufacture of lentiviral vectors” gives advice regarding quality and safety of the vectors [24].

Importantly, the specific safety aspects related to GTMPs have to be considered and analyzed before the products can be used in the clinic. The EMEA “Guideline on the non-clinical studies required before first clinical use of Gene Therapy Medicinal Products” [38] specifies which studies are essential prior to the first application to humans. This includes but is not limited to non-clinical proof of concept studies, biodistribution studies, as well as studies on dose finding, germ line transmission, immunotoxicity and studies addressing the environmental risks/shedding. Specific recommendations for the later are defined in the EMEA “Guideline on scientific requirements for the environmental risk assessment of Gene Therapy Medicinal Products” [39]. This guideline states: "Generally the purpose of clinical trials are to study the adsorption, distribution, metabolism and excretion of one or more Investigational Medicinal Products with the object of ascertaining its (their) safety and/or efficacy ([28]; definition of a clinical trial). As such the evaluation of vector shedding is a requirement for a phase I study.” Data of clinical trials regarding environmental risks need to be collected and integrated in a full environmental risk assessment (ERA) needed for a marketing authorization procedure. Other guidelines dealing with environmental risk assessments of genetically modified organisms are EMEA/BWP/473191/06-corr and EMEA/CHMP/BWP/135148/04.

Furthermore, in terms of studies addressing the risk and ethical concerns of inadvertent germline transmission, separate guidelines are available. The EMEA “Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors” [34] recommends adjusted study designs depending on the type of vector used, as well as providing a decision tree regarding the necessary questions to be addressed by biodistribution and germ line transmission studies. Also a considerations paper of the International Conference On Harmonization Of Technical Requirements For Registration Of Pharmaceuticals For Human Use (ICH) is available on this topic and can be consulted in this regard (ICH considerations, general principles to address the risk of inadvertent germline integration of gene therapy vectors). The ICH S2B document “Note for guidance on genotoxicity” [26], however, gives recommendations for studies to address the risk of genotoxicity and can give advice in these questions.

If patients have been treated with a gene therapy approach in a clinical trial, clinical monitoring as well as intensive follow-up care should be performed in order to detect adverse events at an early stage to avoid clinical implications and to collect safety data. The “Guideline on follow-up of patients administered with Gene Therapy Medicinal Products” [41] gives recommendations in this regard.

Regulation (EC) No 726/2004 already regulates the marketing authorization procedure of biotechnology medicinal products on the European level. In this context, the products pass through a centralized authorization procedure at the EMEA in order to assess their quality, safety and efficacy. The technical requirements needed to prove the latter are defined in Annex I to Directive 2001/83/EC.

Nevertheless, the complexity and variety of ATMPs may result in a situation of very specific and individual questions to be addressed. Within the scope of the ‘ATMP regulation’, the Committee for Advanced Therapies (CAT) will be established within the EMEA in order to provide strong expertise in this field and exhibit draft opinions on ATMP applications presented to EMEA [50, Chapter 7]. Therefore, Regulation (EC) No 726/2004 needs to be amended. Currently, the CAT is in the process of establishment within the EMEA. Updated details can be found on the respective webpage of EMEA. Within the context of a marketing authorization, the standards for pharmacovigilance described in Regulation 726/2004 apply. Since clinical trials are typically powered for efficacy and furthermore the duration of the respective trials might not allow the detection of long term adverse events, the application has to provide a plan to ensure the follow-up of adverse reactions after marketing authorization. A specific EMEA guideline giving further recommendations on “Safety and Efficacy Follow-Up – Risk management of Advanced Therapy Medicinal Products” is already published [33]. Another measure of safety is the full traceability of the product (including the starting materials) and the treated patient. According to the ‘ATMP regulation’, the marketing authorization holder for an ATMP is responsible for setting up a traceability system [50, Article 15]. If human tissues or cells are involved, the traceability standards defined in Directive 2004/23/EC also apply, as do the requirements of Directive 2002/98/EC concerning human blood and blood components, respectively.

Finally, it should be noted that both the European agency EMEA and the German agency PEI (in charge of ATMPs) provide scientific advice. Investigators are welcome to consult the agencies in all phases of project development in order to obtain important project-specific advice, e.g., before applying for a clinical trial or marketing authorization. Details can be found on the webpages of EMEA or PEI, respectively.

Outlook

Application of new technologies of gene therapy to the treatment of diseases will yield the greatest benefits if approached on a sound scientific and medical basis. Regulatory guidelines are the basis of (i) current scientific knowledge, (ii) scientific expertise in a given research area, and (iii) the result of a continuous interaction between researchers and regulatory experts. Gene therapy has entered the stage of clinical evaluation. As always at the frontier of bench to bedside research, patient safety must be the first and foremost consideration in human gene therapy before one enters the stage of extensive clinical trials to assess efficacy.

References

Index of scientific references

1. Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118(9):3132-3142.

2. Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118(9):3143-50.

3. Boehm T, Foroni L, Kaneko Y, et al. The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc. Natl. Acad. Sci. 1991;88:4367–4371.

4. Royer-Pokora B, Loos U, and Ludwig WD. TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukemia with the t(11;14)(p13;q11). Oncogene. 1991;6:1887–1893.

5. Baum C, Schambach A, Bohne J, and Galla M. Retrovirus Vectors: Toward the Plentivirus? Mol Ther. 2006;13:1050-1063.

6. Wu X, Li Y, Crise B, and Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science. 2003;300(5626):1749-1751.

7. Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446:758-764.

8. Modlich U, Bohne J, Schmidt M, et al. Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood. 2006;108:2545-2553.

9. Zychlinski D, Schambach A, Modlich U, et al. Physiological Promoters Reduce the Genotoxic Risk of Integrating Gene Vectors. Mol Ther. 2008;16(4):718-725.

10. Emery DW, Yannaki E, Tubb J, et al. Development of virus vectors for gene therapy of beta chain hemoglobinopathies: flanking with a chromatin insulator reduces gamma-globin gene silencing in vivo. Blood. 2002;100:2012-2019.

11. De Palma M, Montini E, Santoni de Sio FR, et al. Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells. Blood.2005;105(6):2307-15.

12. Chong H, Starkey W, and Vile RG. A replication-competent retrovirus arising from a split-function packaging cell line was generated by recombination events between the vector, one of the packaging constructs, and endogenous retroviral sequences. J Virol.1998;72:2663–2670.

13. Marshall E. Gene therapy. Viral vectors still pack surprises. Science. 2001;294(5547):1640.

14. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342-7.


Index of regulatory references

15. 3. Notification (“3. Bekanntmachung”) of the Federal Institute for Drugs and Medical Devices and the Paul Ehrlich Institute of 10 August 2006 on the clinical trial of medicinal products for human use.

16. Commission Directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use. OJ L 159, 27.06.2006, p.46.

17. Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use.OJ L 262, 14.10.2003, p.22.

18. Commission Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components. OJ L 91, 30.03.2004, p.25.

19. Commission Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards traceability requirements and notification of serious adverse reactions and events. OJ L 256, 01.10.2005, p.32.

20. Commission Directive 2005/62/EC of 30 September 2005 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications relating to a quality system for blood establishments. OJ L 256, 01.10.2005, p.41.

21. Commission Directive 2006/17/EC of 8 February 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells. OJ L 38, 09.02.2006, p.40.

22. Council Directive 90/385/EEC  of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices. OJ L 189, 20.07.1990, p.17

23. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. OJ L 169, 12.07.1993, p.1.

24. CHMP/BWP/2458/03 of the Committee for Medicinal Products for Human Use (CHMP) of 26 May 2005. Guideline on development and manufacture of lentiviral vectors.

25. CPMP/BWP/3088/99 of the Committee for Proprietary Medicinal Products (CPMP) of 24 April 2001. Note for Guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products.

26. CPMP/ICH/174/95 ICH Topic S 2 B of March 1998. Genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals, Step 5. Note for guidance on genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals.

27. CPMP/ICH/291/95 ICH Topic E 8 of March 1998. General considerations for clinical trials, step 5. Note for guidance on general considerations for clinical trials.

28. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJ L 121, 1.5.2001, p.34.

29. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. OJ L 311, 28.11.2001, p.67.

30. Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood componentsand amending Directive 2001/83/EC. OJ L 33, 08.02.2003, p.30.

31. Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. OJ L 102, 07.04.2004, p.48.

32. Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market.

33. EMEA/149995/08 of the Committee for Medicinal Products for Human Use (CHMP) of 20 November 2008. Guideline on safety and efficacy follow-up – risk management of advanced therapy medicinal products.

34. EMEA/273974/05 of the Committee for Medicinal Products for Human Use (CHMP) of 16 November 2006. Guideline on non-clinical testing for inadvertent germline transmission of gene transfer vectors.

35. EMEA/CHMP/410869/06 of the Committee for Medicinal Products for Human Use (CHMP) of 21 May 2008. Guideline on human cell-based medicinal products.

36. EMEA/CHMP/BWP/135148/04 of the Committee for Medicinal Products for Human Use (CHMP) of 20 January 2005. Environmental risk assessments for medicinal products containing, or consisting of, genetically modified organisms (GMOs) (Module 1.6.2).

37. EMEA/CHMP/BWP/473191/06 - Corr of the Committee for Medicinal Products for Human Use (CHMP) of 11 December 2006. Guideline on environmental risk assessments for medicinal products consisting of, or containing, genetically modified organisms (GMOs).

38. EMEA/CHMP/GTWP/125459/06 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Guideline on the non-clinical studies required before first clinical use of gene therapy medicinal products.

39. EMEA/CHMP/GTWP/125491/06 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Guideline on scientific requirements for the environmental risk assessment of gene therapy medicinal products.

40. EMEA/CHMP/GTWP/405681/06 of the Committee for Medicinal Products for Human Use (CHMP) of 24 May 2007. Concept paper on the development of a guideline on the quality, preclinical and clinical aspects of medicinal products containing genetically modified cells.

41. EMEA/CHMP/GTWP/60436/07 of the Committee for Medicinal Products for Human Use (CHMP) of 30 May 2008. Draft guideline on follow-up of patients administered with gene therapy medicinal products.

42. Eudralex Volume 4. Good manufacturing practice guidelines. Volume 4 of “The rules governing medicinal products in the European Union”. http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol4_en.htm

43. European Pharacopoeia. http://www.pheur.org

44. GCP Ordinance (“GCP-Verordnung“). Of the German Federal Ministry for Health and Social Security of 09 August 2004 for good clinical practice in the conduct of clinical trials on medicinal products for human use. Federal Law Gazette I, 12.08.2004, p.2081.

45. German Act on Medical Devices (“Medizinproduktegesetz”) of the Federal Republic of Germany of 02.08.1994 in the version of the notification of the Law of 07.08. 2002. Federal Law Gazette I p.3146.

46. German Tissue Act (“Gewebegesetz“) of the German Federal Parliament of 20 July 2007 on the quality and safety of human tissues and cells. Federal Law Gazette I, 27.07.2007, p.1574.

47. ICH Considerations of the International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use of 25 October 2006. General principles to address the risk of inadvertent germline integration of gene therapy vectors.

48. Medicinal Products Act (“Arzneimittelgesetz”) of the Federal Republic of Germany of 24.08.1976 in the version of the notification of the Law of 12th December 2005. Federal Law Gazette I p.3394.

49. Ordinance for the manufacture of medicinal products and active pharmaceutical ingredients (“AMWHV”) of the German Federal Ministries for Health and Food, Agriculture and Consumer Protection of 03 November 2006. Federal Law Gazette I, 09.11.2006, p.2523.

50. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. OJ L 324, 10.12.2007, p.121.

51. Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. OJ L 136, 30.04.2004, p.1.

52. Transfusion Law (“Transfusionsgesetz”) of the Federal Republic of Germany of 01.07.1998 in the version of the notification of the Law of 28.08.2007. Federal Law Gazette I p.2169.

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Велькель К., Люрманн А., Баум К., фон дер Ляйен Х.Э.

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Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта. <br /><br />Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов. <br /><br />Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. <br /><br />Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(6265) "

Генная терапия предназначена для лечения генетических дефектов путем введения корригированной копии мутантного гена. Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта.

Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов.

Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. 

Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования.

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Christine Voelkel1,2, Anke Lührmann2, Christopher Baum1,3, and Heiko E. von der Leyen2

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1Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;
2Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany;
3Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA


Correspondence
Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany,
Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: vdleyen@spam is badclinical-trial-center.de

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Retrovirus mediated gene therapy has already proven to be more than just a theoretical option to treat patients with severe genetic defects. Clinical gene therapy trials of X-linked severe combined immunodeficiency or adenosine deaminase deficiency have demonstrated the success and potential benefit of the therapy. Nevertheless, the complexity of the therapeutic products and their biological origin, as well as virus-related safety concerns require the need of a strict regulatory framework in order to guarantee the quality of the individual products and safety of the patients. The aim of this review is to give an overview of the rapidly evolving regulatory framework of Advanced Therapy Medicinal Products in Europe. We will summarize the most important regulatory documents to be considered before entering the clinical development phase – not only from a German but also from a European perspective.

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Retrovirus mediated gene therapy has already proven to be more than just a theoretical option to treat patients with severe genetic defects. Clinical gene therapy trials of X-linked severe combined immunodeficiency or adenosine deaminase deficiency have demonstrated the success and potential benefit of the therapy. Nevertheless, the complexity of the therapeutic products and their biological origin, as well as virus-related safety concerns require the need of a strict regulatory framework in order to guarantee the quality of the individual products and safety of the patients. The aim of this review is to give an overview of the rapidly evolving regulatory framework of Advanced Therapy Medicinal Products in Europe. We will summarize the most important regulatory documents to be considered before entering the clinical development phase – not only from a German but also from a European perspective.

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1Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;
2Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany;
3Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA


Correspondence
Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany,
Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: vdleyen@spam is badclinical-trial-center.de

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1Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;
2Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany;
3Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA


Correspondence
Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany,
Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: vdleyen@spam is badclinical-trial-center.de

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Велькель К., Люрманн А., Баум К., фон дер Ляйен Х.Э.

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Велькель К., Люрманн А., Баум К., фон дер Ляйен Х.Э.

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["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13490" ["VALUE"]=> array(2) { ["TEXT"]=> string(6323) "<p class="bodytext">Генная терапия предназначена для лечения генетических дефектов путем введения корригированной копии мутантного гена. Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта. <br /><br />Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов. <br /><br />Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. <br /><br />Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(6265) "

Генная терапия предназначена для лечения генетических дефектов путем введения корригированной копии мутантного гена. Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта.

Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов.

Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. 

Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования.

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Генная терапия предназначена для лечения генетических дефектов путем введения корригированной копии мутантного гена. Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта.

Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов.

Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. 

Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования.

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Introduction

Multiple studies have been performed investigating the kinetics, safety and efficiency of mesenchymal cell isolation, characterization, culture-expanding, and clinical approaches [26, 10, 1, 31, 14, 18, 21, 27, 28]. In recent years the biological activity of MSC has been very actively discussed for their potential use for suppression of autoimmune and transplant-related reactions, but also with the aim of speeding up of hematopoiesis recovery after bone marrow transplantation [15, 16, 29, 24]. Many existing protocols suppose the use of autologous MSCs [23, 9].  However, the use of autologous MSCs may be limited in a clinical setting, due to imperfect and often controversial knowledge of the functional competence and integrity of immunosuppressive and hematopoietic-supporting potentials of these cells [19, 5, 8, 4]. As shown earlier, bone marrow-derived mesenchymal stromal stem cells provide support for hematopoiesis in vitro and in experimental animal models [3, 15, 16, 24]. In this study we compared the morphology, immunophenotype, and immunoregulatory activities of MSCs derived from the bone marrow of healthy donors and patients with hematological malignancies. Our results demonstrated that MSCs derived from bone marrow suffering from hemoblastoses can be successfully expanded in culture and infused along with PBSCs after high-dose chemotherapy without any toxicity. Moreover, one of the promising results is the decrease in the period of critical neutropenia and thrombocytopenia in the patient after high-doses chemotherapy, when PBSCs and MSCs are co-transplanted. Our results show that co-transplantation of MSCs is associated with rapid hematopoietic recovery when PBSC counts are suboptimal.

Patients and methods

From April 2005 through June 2007, after obtaining written informed consent, 39 patients who were eligible for high-dose chemotherapy and PBSC transplantation were enrolled into single center investigation of the feasibility, safety, and hematopoietic effects of autologous culture-expanded MSCs (Table 1). The clinical trial protocol and the consent form were approved by the Local Ethics committee of the Institute of Clinical Immunology SB RAMS.

Table 1. Characteristics of patients who were treated with (n=39) and without (n=42) mesenchymal stem cells

Control

MSC supported

Median age, years (range)

32 (17–57)

31 (7–55)

Gender (male/female)

16/23

22/21

Diagnoses

HD

CR 4
PR 8
Refractory 3

CR 0
PR 5
Refractory 3

NHL

CR 4 
PR 2
Refractory 2

CR 4
PR 6
Refractory 4

MM

CR 2
PR 2
Refractory 3

CR 0
PR 2
Refractory 2

AML (1st remission)

2

11

ALL  (2nd remission)

4

4

SLE (SLEDAI >16)

3

2

Conditioning regimens

BEAM for HD and NHL;
mono-Melphalan 140–200/m2 for AML, ALL and MM;
Cyclophosphamide 120 mg/kg for SLE

Mean dose of CD34+/CD45+ cells

5.57/kgx106(1.81–9.5x106/kg)

5.64/kgx106(2.5–8.7x106/kg)

Mean dose of MSCs

--

6.64x106 (0.8–23.0x106)

 

Patients with lymphomas and leukemia were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and were required to have adequate visceral organ function, including a left ventricular ejection fraction of at least 50%, forced expiratory volume in 1 second, serum direct bilirubin less than 2.0 mg/dl, and an actual or calculated creatinine clearance greater than 60 ml/min. Also all patients with hematological diseases underwent restaging evaluation with blood count, biochemical activity, trepanobiopsy, and computed tomography.

At the start of therapy, a neutrophil count greater than 1.2x106/ml and a platelet count greater than 100x106/ml were required. Patients were excluded if they had bone marrow involvement or active infection. Patients were excluded for evidence of tumor on routine histological staining of bilateral paraffin-embedded posterior iliac crest bone marrow biopsy specimens. In the “refractory group”, the patient was required to have no effects after standard chemotherapy.

SLE patient eligibility depended on a refractory to standard immunosuppression therapies and either organ- or life-threatening visceral involvement. The inclusion criteria were: not controlled with pulse therapy Cy glomerulonephritis (World Health Organization (WHO) class III–IV), central nervous system (CNS) lupus, vasculitis involving the lung or heart, or transfusion-dependent autoimmune cytopenias. Evaluation of eligible patients by two independent rheumatologists and transplant physicians, informed consent, and approval by the ethical committee were part of the protocol of Tyndall et al. [29]

High-Dose Chemotherapy and PBSC Infusion

The PBSC mobilization regimen consisted of Cyclophosphamide 4.0 g/m2 IV infusion over 6 hours on day 1, along with Mesna (first 3.0 g/m2 IV, then 500 mg every 3 hours orally/IV for eight doses). On day 7 after completion of the Cyclophosphamide, patients began subcutaneous injections of recombinant human G-CSF (Neupogen, Granocyte, Leukostim) 10 mg/kg/d. On recovery of neutrophils to a level greater than 1.2x109/l (usually 12 to 15 days after Cyclophosphamide treatment), patients underwent a leukapheresis procedure using AS TEC 204 (Fresenius, Germany) or Spectra LRS 07 (COBE, Lakewood, CO) apheresis equipment. Cells were cryopreserved using a controlled-rate liquid nitrogen freezer using previously published methods [10]. After PBSC procurement, high-dose chemotherapy with BEAM (BCNU 300 mg/m2 on day -7, Etoposid 800 mg/m2 and Ara-C 800 mg/m2 on days -6, -5, -4, -3, Melphalan 120 mg/m2 on day -2) for NHL and HD patients, Alceran (200 mg/m2 on day -2) for patients with AL, Cy (200-140 mg/kg in divided doses for 4 days -6, -5, -4, -3 with/or not ATG (total doses 60 mg/kg) for patients who suffered from SLE were administered. PBSCs were thawed and infused 24 hours after the completion of high-dose chemotherapy.

Phenotypic analysis of mobilized cells (expression of CD 34 and CD45) was performed using multicolor flow cytometry (FACSCalibur, Becton Dickinson). Moreover, cancer cell contamination of every PBSC specimen was excluded by the use of cytological analysis.

Supportive Care

Before, during, and for 24 hours after treatment with high dose Cyclophosphamide, patients received hyperhydration with forced diuresis and Urometexan (Mesna) infusion for the prevention of hemorrhagic cystitis. Patients were treated in a single room without air filtration. All patients followed a standardized supportive care protocol including antiemetic therapy, analgesia for mucositis, transfusion support, and venoocclusive disease prophylaxis. A low microbial diet, oral daily Fluoroquinolone (1 g/d) changed to intravenous Cefepime on neutropenic fever, Fluconazole (400 mg/d) and Acyclovir (10 mg/kg/d) and aerosolized Amphotericin B (10 mg twice daily) were started upon admission and discontinued when the ANC rebounded to 0.5x109/l. Platelets irradiated with 25 Gy and red blood cells were given to maintain a platelet count greater than 20 000/μl and a hemoglobin level greater than 8.0 g/dl. For the first 6 months after transplantation, patients were treated orally with daily oral Fluconazole and Trimethoprim/Sulfamethoxazole three times a week.

Harvesting and Ex Vivo MSC Culture

A median of 50 ml of bone marrow aspirate was obtained under sterile conditions by puncture of posterior iliac crests of patients or donors (n=9) under local anesthesia during standard pre-transplant staging approximately 2 days before high-dose Cyclophosphamide mobilization and 30 days before scheduled PBSC infusion. Washed heparinized bone marrow cells were re-suspended in phosphate-buffered solution (PBS, Sigma-Aldrich, Germany) and overlaid on Ficoll density gradient (1.078 g/l), then centrifuged for 20 min at 1000 g. A median of 320x106 (range 250–600 x106) mononuclear cells (MNC) were collected from the interface, washed three times in PBS, and re-suspended in α-modified minimum essential medium (αMEM, Sigma-Aldrich, Germany) containing 100 μg/ml gentamycin and 5% human platelet lysate (PL). After the cell number was counted, 30 ml of cell suspension was plated in a 175 cm2 plastic culture flask (Nunc, Denmark).

It is important to note that for clinical use with a therapeutic intent we used 5% platelet lysate to replace fetal calf serum (FCS) in the MSC culture. Platelet lysate was obtained from several allogeneic platelet units prepared by machine trombocytaphereis using AS TEC 204 (Fresenius, Germany). The platelet units were frozen at -40 C, thawed, mixed, aliquoted and lysate frozen at -20 C until use.

MSCs were cultured in humidified incubators with 5% CO2 and initially allowed to adhere for 72 hours, followed by a media change every 3 days. When cultures reached more than 90% confluence, adherent cells were detached with 0.05% trypsin-EDTA (Sigma-Aldrich, Germany) and replated at a density of 0.8x106 per 175 cm2 flask until processing for cryopreservation. Harvested MSCs from 1-2 passages were cryopreserved with a rate-controlled freezer (Planer Kryo 560-16) in 10% human Albumin solution (Microgen, Russia) and in a final concentration of 10% Dimethylsulfoxide (Sigma-Aldrich, Germany) and 10% Hydroxyethylstarch in freezing bags. 

Cell cultures were tested for sterility weekly and before cryopreservation (Municipal Hospitals N1, Microbiology Laboratory, Novosibirsk) for the presence of bacterial/fungal contamination via microbiological cultural tests. All cell manipulations were performed in a sterile class II biological safety cabinet.

The number of MSCs was estimated by the quantity of colony forming unit-fibroblasts (CFU-F). For that, 106 of bone marrow MNCs were cultivated in Petri dishes for 14 days and stained using Giemsa protocol, then the number of spindle-shaped cell colonies consisting of more than 50 cells were counted.

Flow Cytometry

Phenotypic analysis of MSCs (expression of CD3, CD14, CD16, CD20, CD34, CD73, CD90, CD105 and HLA-DR molecules) was performed using multicolor flow cytometry (FACSCalibur, Becton Dickinson). Cells were detached with 0.05% trypsin-EDTA (Sigma, USA), washed with PBS plus 2% bovine albumin, fixed in 1% paraformaldehyde, blocked with 10% normal goat serum, and incubated separately with appropriate primary antibodies (BD Bioscience, USA). Non-treated MSCs were used as negative control.

The immunosuppressive properties of MSCs

To study MSC effects on immune cell function, MSCs were first cultivated for 24 h in flat-bottomed 96-well or 24-well plates in α-MEM/20% fetal calf serum (FCS, Gibco, USA). After this, peripheral blood MNCs (PBMNCs) from donors were added to MSC monolayer and stimulated with mitogens or alloantigens (mixed lymphocyte culture, MLC). For MLC, 0.1x106 PBMNCs from two donors were cultivated for 5 days in RPMI-1640 medium supplemented with 0.3 mg/ml L-glutamine, 100 μg/ml Gentamycine and 10% of heat-inactivated donor AB (IV) serum. Mitogen-induced proliferative response was studied in 3-day cultures of donor PBMNCs, which were activated by Concanavalin A (ConA, 15 μg/ml, Sigma-Aldrich, Germany) or 1 μg/ml monoclonal antibodies against CD3 (anti-CD3, Becton Dickinson, USA). Cell proliferation was measured by incorporation of 3H-thymidine that was added at 1 μCi/well during  the last 18 h of cultivation. Proliferative response of MNCs cultivated without MSCs was used as control.

Support for hematopoiesis by MSC (CFU Assay)

To estimate MSCs' effect on colony-forming activity of hematopoietic progenitor cells, bone marrow MNC were grown in “complete” methylcellulose medium (Methocult H4344, Stem Cell Technologies, Vancouver, BC), containing hSCF, hGM-CSF, hIL-3, and hEPO at a density of 25x105/ml. Autologous MSC were added to MNCs in MNC: MSC ratios of 1:1 and 10:1 in triplicates. Cultures were grown at 37°C, 5% CO2 for 14 days, then the numbers of erythroid- and granulocyte-macrophage colony-forming units (CFU-E and CFU-GM, respectively) were calculated. Colonies were considered if consisted of at least 50 cells.

MSC Infusion

On the day of infusion, cryopreserved units were thawed ex tempore in a 37°C water bath, washed twice with PBS, transferred into 60-ml syringes with 10% human Albumin and infused into patients one hour after the PBSC infusion through a side port of a running 0.9% saline IV infusion into a central catheter over 10 to 20 minutes. Patients were premedicated with Acetaminophen (650 mg) and Diphenhydramine. Vital and clinical signs and symptoms were monitored at the time of infusion and every 15 minutes thereafter for 3 hours, followed by every 2 hours for 6 hours and every 8 hours for 3 days. There was no immediate or delayed toxicity related to MSC infusion. None of the patients experienced allergic reactions or respiratory symptoms.

Statistical analysis

Statistica 6.0 software for Windows, StatSoft Inc. USA was used for basic descriptive, and correlation analysis of data. The statistical significance was assessed with the Mann-Whitney U-test. The T-test was used to analyze the difference in means when comparing two groups. In assessing correlation, we used 2D scatterplots estimated correlation coefficient r and P-value for Rank Order Correlation Spearmen test. A p-value of less than 0.05 was considered statistically significant.

Results

MSC characteristics

At the first stage we compared the quantity of MSCs in bone marrow of patients with hemoblastosis and healthy donors. Since MSCs were first described as fibroblast-like cells capable of forming colonies 13], the initial content of MSC precursors among bone marrow MNCs was measured as a colony-forming unit fibroblast (CFU-F) number. The mean number of CFU-F in the control group was 36±3 colonies per 106 bone marrow-derived MNCs (min-max range 16–70). The CFU-F number in patients with hemoblastosis was 21±3 (p<0.05). The range of values in the patient group widely varied (from 1 to 67 CFU-F), and 70% of samples showed CFU-F numbers that were below the lower quartile value of control group (<25 CFU-F). The most significant decrease of CFU-F number was revealed in patients with NHL (16±5, p<0.01). In patients with MM and HL number of MSC precursors was also decreased (19±10 and 26±7, respectively; p>0.05). Decreasing CFU-F numbers mean that MSC progenitors in bone marrow of investigated patients are present at a lower amount.

Taking into consideration the MSC deficiency in patients with hemoblastosis, it seemed important to evaluate their ability for expansion in vitro. With that aim we analyzed the growth rate of MSC by measuring cultivation time until confluence. In healthy volunteers, confluent growth in MSC cultures was reached by day 15±0.5 (range 11–22 days). Meanwhile, in the patient group 80–90% confluence took on average 26±2 days (range 10–50); 23±3 days in patients with HL (p<0.01); 29±3.5 days in patients with NHL (p< 0.01), and 30±4 days in patients with MM (p<0.01). It seems to be important that despite a low CFU-F number in patient cultures it was possible to isolate and in vitro expand MSCs from patients with hematological malignancies.

MSC immunophenotype

Further, we characterized the immunophenotype of MSCs. Classically, MSCs are defined as cells expressing STRO-1, CD105 (SH2), CD71, CD73 (SH3, SH4), CD90 (Thy1) surface markers and not expressing lineage (CD3, CD14, CD20, CD16) and hematopoietic (CD34, CD45) markers along with HLA-DR antigen [11, 30]. We observed that on the first passage the MSCs of healthy volunteers expressed  CD73 (88±3.7%), CD90 (83±2.6%) and CD105 (90±6.3%), while only some few MSCs expressed CD34 (0.7±0.3%), CD3 (3.9±1.5%), CD20 (5.3±2.3%), CD16 (5.6±1.7%), CD14 (5.6±2.3%), and HLA-DR (11.1±1.6%).

The MSCs of patients with ALL, HL, NHL and MM were found to express a similar immunophenotype. However, several differences were revealed as well. Firstly, CD73, CD90 and CD105-positive cells were lowered (78±6.8, 71±8.7 and 82±10% correspondingly; p>0.05). Secondly, in contrast to healthy volunteers, MSCs of patients with hemoblastosis showed a two-fold increased number of HLA-DR-positive cells (23±4.8 vs 11.1±1.6%, p<0.05), which is in agreement with published data [6].

Immunosuppressive properties of MSCs

Evaluation of the immunosuppressive activity of MSCs showed that donor MSCs rendered a dose-dependent suppressive effect on T-cell proliferation in mixed lymphocyte cultures (Fig. 1) as well as in cultures stimulated with ConA or monoclonal anti-CD3 antibodies (data not shown). The most pronounced effect was observed at the MSC:MNC ratio of 1:1. However, even at lower concentrations of MSCs (MSC:MNC ratio of 1:2 and 1:4) their suppressive activity remained high, and averaged 44–47%. In patients with hemoblastosis a significant suppressive effect of MSCs was registered only at the highest concentration of MSCs in culture (MSC:MNC ratio of 1:1). Nevertheless, even in this case the level of immunosuppressive activity of patient MSCs was lower compared to the level in control group (52±7 and 72±18%, correspondingly; p>0.05), varying from 18 to 64%. Reduction of MSC dose in mixed lymphocyte cultures strongly decreased ability of MSCs to block T-cell proliferative response.

2009-4-en-Sergeevicheva-et-al-Figure-1.JPG

Figure 1. Effects of donor and patient MSCs on proliferative response of T-cells in MLC.
MNCs from two donors (both 0.1x106 per well) have been cultivated for 5 days in the absence (control) or presence of MSCs of healthy donors (n=7) or hematologic patients (n=10). Cellular uptake of 3H-thymidine added at 18 hours before the end of cultivation was used to measure cell proliferation rate. Results are expressed as a suppression rate in percents calculated using the following formula: Sergeevicheva-fig1-formula.jpg, where cpmMNC+MSC is proliferation rate of MNCs in presence of MSCs, and cpmMNC is proliferation rate of MNCs in absence of MSCs (control).

Support of hematopoiesis by MSC

One of the promising fields of therapeutic application of MSCs is their use for the rapid recovery of hematopoiesis after bone marrow transplantations. This statement is based on the ability of mesenchymal cells to support the hematopoietic progenitors [9, 15]. However, the question about the integrity of hematopoiesis-supporting potential of MSCs in case of hemoblastosis still remains open. Assessment of the colony-forming potential of patient bone marrow MNCs under co-incubation with autologous MSCs showed that the presence of MSCs (in ratio of 1:1) increased the number of CFU-E and CFU-GM approximately five times (Fig. 2). It should be noted that even in the presence of lower MSC concentration (in ratio of 1:10) a two-fold increase of hematopoietic colonies was also registered. The ability of MSCs to support hematopoietic progenitors in vitro was observed in all investigated cases (ALL, n=3; HL, n=3; NHL, n=3).

2009-4-en-Sergeevicheva-et-al-Figure-2a.JPG

Figures 2a/b. Effects of MSCs on colony-forming activity of bone marrow MNCs.
Bone marrow MNCs of hematologic patients (n=9) were cultivated for 14 days in absence (control) or presence of autologous MSC at various concentrations (1:1 and 1:10) in semi-liquid methylcellulose medium. At the end of cultivation the amounts of erythroid (A) and granulocyte-macrophage (B) colonies per 105 MNCs were calculated.    * - pU < 0,05 and ** - pU < 0,01 – versus control; Mann-Whitney U-test.


2009-4-en-Sergeevicheva-et-al-Figure-2b.JPG

Hematopoietic engraftment and clinical outcome

Patients of both groups received a PBSC infusion containing equal doses of CD34+cells: the mean number of CD34+ mononuclear cells was 5.57х106/kg in the control group and 5.64х106/kg in the group with MSC co-transplantation. The dose of mesenchymal cells infused varied from 0.8x106 to 23x106 (mean 6.64x106).

2009-4-en-Sergeevicheva-et-al-Figure-3.JPG

Figure 3. Effects of MSCs infusions on neutrophil recovery. The t-test was used to evaluate a difference in period of neutrophil recovery.


2009-4-en-Sergeevicheva-et-al-Figure-4.JPG

Figure 4. Effects of MSCs infusions on neutrophil recovery. The t-test was used to evaluate a difference in period of platelets recovery.

There was no significant correlation between the number of MSCs and days of neutropenia or thrombocytopenia. However, we found a significant invert correlation between the number of MSCs and days of neutropenia in selected group, when infused PBSC were <3.0x106/kg.

No differences in analysis of severity and rate of complication, transfusion dependence, total or disease-free survival between the groups compared were revealed. Patients underwent standard restaging evaluation with computed tomography 42 days after transplantation and every 3 months thereafter. All patients evaluated on Day +60 were free of symptoms and clinical findings. Median follow-up of the patients is 9 months (range 4 to 22 months). Four patients died as a result of early disease progression (NHL, n= 2; HD, n=1; MM, n=1). All of them had refractory disease before PBSC transplantation. Of the 34 remaining patients, 33 are without evidence of disease; one has a stable disease (plato-phase in MM).

Transplant-related mortality / Toxicity

Two patients died on Day +7 and +21 due to transplant-related complications. There was one patient who died before engraftment. The cause of death in patient 1 on Day +7 was pneumonia and Candida sepsis as background. Patient 2 recovered hematopoiesis on Day +11, but died from pneumonia on Day +21. Progression of HD: lymphoadenopathy in the mediastinum was also revealed on autopsy of patient 2. Similar toxicity and causes of death were found in the control group: 3 fatal outcomes due to infection among 42 transplanted patients.

Discussion

The work presented here originated from the question of whether MSCs isolated from bone marrow of patients with hematologic malignancies possess intact functional properties including immunosuppressive activity and hematopoiesis-supporting ability. The transplantation of autologous bone marrow is widely used in clinical practice, but very little data exists on the characteristics of MSCs from the bone marrow of these patients, and the reported results often differ from one other.

Some authors have shown a statistically significant decrease of CFU-F numbers in cases of acute myeloid leukemia either in primary patients and patients after PCT courses [5, 6, 8] or for patients suffering from lymphomas, acute lymphoid leukemia and multiple myeloma [6, 23]. Notable is that the CFU-F number in patients varies from total absence to donor values. Moreover, neither sex nor age or involvement of bone marrow or time of the last PCT course affects the number of CFU-F [23]. In this study we also found a decrease in the CFU-F numbers for bone marrow samples obtained from patients with hemoblastosis. However, despite a low CFU-F number in patients our data display the principal possibility of isolation and in vitro expansion of MSC from patients with hematological malignancies.

Moreover, our results demonstrated a decrease in the proliferative capacity of in vitro expanded patient MSCs. For achieving confluence growth of patients’ MSCs, cultivation time needed to be twice as long. On the one hand, this may be caused by inhibition of proliferative potential in the patients’ MSCs, and on the other hand it may be caused by initially lowered content of MSC in bone marrow MNCs under hematological malignancies.

Our data shows that the MSCs of patients with ALL, HL, NHL, and MM do not express linear and hematopoietic antigens but are positive for some “stromal” markers. Along with that we managed to elicit some other special features. Namely, in the MSC population there was a lower number of CD73, CD90, and CD105-positive cells. Moreover, patient MSCs exhibited a two-fold increased number of HLA-DR-positive cells. Our data corresponds with Campioni D. et al [6], who used 4-color flow cytometry to show significant decreases in CD73, CD90, and CD105 expression on MSCs of 43 hematological patients. We have found this fact just as a tendency but this probably was caused by small array of patients (n=16) or by using 1-2-color flow cytometry.

We further found that in contrast to donor cells, patient MSCs in some cases did not suppress but even increased a proliferative response in MLC (data not shown), which corresponds with published data [17]. The low number of such observations did not allow us to connect this feature either with a distinct nosologic form of hemoblastosis, nor with particular phenotype or morphology of MSCs. One of the possible reasons for this phenomenon could be the ability of MSCs to secrete IL-7, which induces and supports lymphocyte proliferation [9].
 
Finally, in all investigated cultures (ALL, HL, NHL) we observed the ability of MSCs to support growth of hematopoietic progenitors in vitro. Published data concerning this issue can not be called univocal. For example, it was demonstated that the stromal cells of patients with acute myeloid leukemia possessed a low potential to stimulate growth of allogeneic hematopoietic precursors [8]. Meanwhile Mayani et al. [19] have shown that stromal cells of patients with AML display intact hematopoiesis-supporting activity, which strongly depends on the presence of CFU-F.

Summarizing the given experimental data we can conclude that MSCs of patients with hemoblastosis used in our study correspond to the Minimal criteria for defining multipotent mesenchymal stromal cells settled in the International Society for Cellular Therapy position statement [11]. These cells are characterized by adhesiveness, show fibroblast-like morphology, and a specific phenotype. Moreover, patients' MSCs display immunosuppressive and hematopoiesis-supporting activity. However, they have a number of distinct features. For instance, patient stromal cells in comparison with healthy donor cells contain lower numbers of CD73, CD90, and CD105-positive cells and a two-fold increased number of HLA-DR-positive cells. In addition, MSCs in hemoblastosis display lower levels of suppressive activity that is only become apparent at high concentrations of MSCs. It is important to note that described features of MSCs in hemoblastosis are not crucial for their hematopoiesis-supporting activity. This fact in combination with the ability of MSCs to expand ex vivo represents the basis for the clinical application of hematopoietic stem cell co-transplantation with mesenchymal stromal cells in oncohematology for the acceleration of hematopoiesis recovery.

Based on our clinical findings, we propose that culture-expanded autologous MSCs can be used to improve the rate and quality of hematopoietic engraftment, particularly in patients who previously received stroma-damaging therapy. Indeed, our report demonstrates that autologous MSCs can be successfully culture-expanded in FCS-free conditioning media, and infused IV for therapeutic intent with efficacy and without toxicity into different nosologic groups of patients at the time of PBSC transplantation. We have optimized MSC culture expansion methods to generate optimal numbers of autologous MSCs in a relatively short period of time for clinical use with a therapeutic intent without xenogenic components (e.g., FCS) [7].

Patients treated with high-dose chemotherapy generally experience complete and rapid neutrophil and platelet engraftment when supported with mobilized PBSCs containing >2–3 106 CD34+ cells. On the other hand, patients receiving lower doses of CD34+ cells are at increased risk for delayed platelet engraftment [3, 2].

Unsuccessful mobilization of CD34+ cells is commonly associated with extensive previous therapy, which is also associated with microenvironment damage. Coupled with low doses of CD34+ cells, an abnormal marrow microenvironment increases the risk of delayed engraftment. Sequential use of high-dose chemotherapy is also toxic to the marrow microenvironment, as evidenced by the delayed hematopoietic recovery after transplantation despite infusion of equal numbers of stem cells [12, 20, 22, 25]. Therefore, attempts to protect and improve the bone marrow microenvironment ex vivo are likely to better hematopoiesis engraftment after suboptimal СD34+ transplantation.

In conclusion our results indicate that the proposed cellular therapy protocol is feasible and may have a number of beneficial clinical effects in the setting of hematopoietic stem-cell transplantation. We therefore suppose studying it in more depths in randomized trials.

References

1. Aggarwal S., Pittenger M.F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-1822.

2. Akard L. Optimum methods to mobilize stem cells. J Clin Oncol 2000; 18: 3063.

3. Appelbaum F. The current status of hematopoietic cell transplantation. Annu Rev Med 2003; 54: 491.

4. Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, et al. Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford) 2007; 46:403-408.

5. Campioni D, Lanza F, Moretti S, Dominici M, Punturieri M, Pauli1 S et al. Functional and immunophenotypic characteristics of isolated CD105(+) and fibroblast(+) stromal cells from AML: implications for their plasticity along endothelial lineage. Cytotherapy 2003; 5: 66-79.

6. Campioni D, Moretti S, Ferrari L, Punturieri M, Castoldi GL, Lanza F. Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment. Haematologica 2006; 91:364-368.

7. Capelli C, Domenghini M, Borleri G, Bellavita P, Poma R, Introna M et al. Human platelet lysate allows expansion and clinical grade production of mesenchymal stromal cells from small samples of bone marrow aspirates or marrow filter washouts. Bone Marrow Transplantation 2007; 1–7.

8. Carlo-Stella C, Tabilio A, Regazzi E, Garau D, La Tagliata R, Trasarti S, et al. Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors. Bone Marrow Transplant 1997; 20:465-71.

9. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2000; 28:875-884.

10. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838-3843.

11. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-317.

12. Fried W, Kedo A, Barone J: Effects of cyclophosphamide and of busulfan on spleen colony-forming units and on hematopoietic stroma. Cancer Res 1977; 37:1205-1209.

13. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17:331-340.

14. Gupta P, Blazar BR, Gupta K, Verfaillie CM. Human CD34(+) bone marrow cells regulate stromal production of IL-6 and G-CSF and increase the colony-stimulating activity of stroma. Blood 1998; 91:3724-33.

15. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000; 18:307-316.

16. Le Blanc K , Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439-1441.

17. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003; 57:11-20.

18. Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003; 10:228-241.

19. Mayani H., Guilbert LJ, Janowska-Wieczorek A. Functional characterization of fibroblastic cells in long-term marrow cultures from patients with acute myelogenous leukemia. Leukemia 1993; 7:1564-1569.

20. McManus PM, Weiss L: Busulfan-induced chronic bone marrow failure: Changes in cortical bone, marrow stromal cells, and adherent cell colonies. Blood 1984; 64:1036-1041.

21. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103:4619-4621.

22. Migliaccio A, Migliaccio G, Johnson G, et al: Comparative analysis of hematopoietic growth factor released by stromal cells from normal donors or transplant patients. Blood 1990; 75:305-312.

23. Mueller LP, Luetzkendorf J, Mueller T, Reichelt T, Simon H Schmoll HJ. Presence of mesenchymal stem cells in human bone marrow after exposure to chemotherapy: evidence of resistance to apoptosis induction. Stem Cells 2006; 24:2753-2765.

24. Muguruma Y, Yahata T, Miyatake H, Sato T, Uno T, Itoh J et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood 2006; 107:1878-1887.

25. O’Flaherty E, Sparrow R, Szer J: Bone marrow stromal function from patients after bone marrow transplantation. Bone Marrow Transplant 1995; 15:207-212.

26. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143-147.

27. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T et al.  Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007; 109:228-234.

28. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 2002; 20:530-541.

29. Tyndall A, Fassas A, Passweg J, Ruiz de Elvira C, Attal M, et al.: Autologous haematopoietic stem cell transplants for autoimmune disease — feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and theInternational Stem Cell Project for Autoimmune Disease. Bone Marrow Transplant 1999; 24:729-734.

30. Ucelli A., Moretta L., Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol. 2006; 36:2566-73.

31. Zhang W, Ge W, Li C, You S, Liao L, Han Q et al. Effects of mesenchymal stem cells on differentiation, maturation and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004; 13:263-71.

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Introduction

Multiple studies have been performed investigating the kinetics, safety and efficiency of mesenchymal cell isolation, characterization, culture-expanding, and clinical approaches [26, 10, 1, 31, 14, 18, 21, 27, 28]. In recent years the biological activity of MSC has been very actively discussed for their potential use for suppression of autoimmune and transplant-related reactions, but also with the aim of speeding up of hematopoiesis recovery after bone marrow transplantation [15, 16, 29, 24]. Many existing protocols suppose the use of autologous MSCs [23, 9].  However, the use of autologous MSCs may be limited in a clinical setting, due to imperfect and often controversial knowledge of the functional competence and integrity of immunosuppressive and hematopoietic-supporting potentials of these cells [19, 5, 8, 4]. As shown earlier, bone marrow-derived mesenchymal stromal stem cells provide support for hematopoiesis in vitro and in experimental animal models [3, 15, 16, 24]. In this study we compared the morphology, immunophenotype, and immunoregulatory activities of MSCs derived from the bone marrow of healthy donors and patients with hematological malignancies. Our results demonstrated that MSCs derived from bone marrow suffering from hemoblastoses can be successfully expanded in culture and infused along with PBSCs after high-dose chemotherapy without any toxicity. Moreover, one of the promising results is the decrease in the period of critical neutropenia and thrombocytopenia in the patient after high-doses chemotherapy, when PBSCs and MSCs are co-transplanted. Our results show that co-transplantation of MSCs is associated with rapid hematopoietic recovery when PBSC counts are suboptimal.

Patients and methods

From April 2005 through June 2007, after obtaining written informed consent, 39 patients who were eligible for high-dose chemotherapy and PBSC transplantation were enrolled into single center investigation of the feasibility, safety, and hematopoietic effects of autologous culture-expanded MSCs (Table 1). The clinical trial protocol and the consent form were approved by the Local Ethics committee of the Institute of Clinical Immunology SB RAMS.

Table 1. Characteristics of patients who were treated with (n=39) and without (n=42) mesenchymal stem cells

Control

MSC supported

Median age, years (range)

32 (17–57)

31 (7–55)

Gender (male/female)

16/23

22/21

Diagnoses

HD

CR 4
PR 8
Refractory 3

CR 0
PR 5
Refractory 3

NHL

CR 4 
PR 2
Refractory 2

CR 4
PR 6
Refractory 4

MM

CR 2
PR 2
Refractory 3

CR 0
PR 2
Refractory 2

AML (1st remission)

2

11

ALL  (2nd remission)

4

4

SLE (SLEDAI >16)

3

2

Conditioning regimens

BEAM for HD and NHL;
mono-Melphalan 140–200/m2 for AML, ALL and MM;
Cyclophosphamide 120 mg/kg for SLE

Mean dose of CD34+/CD45+ cells

5.57/kgx106(1.81–9.5x106/kg)

5.64/kgx106(2.5–8.7x106/kg)

Mean dose of MSCs

--

6.64x106 (0.8–23.0x106)

 

Patients with lymphomas and leukemia were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1 and were required to have adequate visceral organ function, including a left ventricular ejection fraction of at least 50%, forced expiratory volume in 1 second, serum direct bilirubin less than 2.0 mg/dl, and an actual or calculated creatinine clearance greater than 60 ml/min. Also all patients with hematological diseases underwent restaging evaluation with blood count, biochemical activity, trepanobiopsy, and computed tomography.

At the start of therapy, a neutrophil count greater than 1.2x106/ml and a platelet count greater than 100x106/ml were required. Patients were excluded if they had bone marrow involvement or active infection. Patients were excluded for evidence of tumor on routine histological staining of bilateral paraffin-embedded posterior iliac crest bone marrow biopsy specimens. In the “refractory group”, the patient was required to have no effects after standard chemotherapy.

SLE patient eligibility depended on a refractory to standard immunosuppression therapies and either organ- or life-threatening visceral involvement. The inclusion criteria were: not controlled with pulse therapy Cy glomerulonephritis (World Health Organization (WHO) class III–IV), central nervous system (CNS) lupus, vasculitis involving the lung or heart, or transfusion-dependent autoimmune cytopenias. Evaluation of eligible patients by two independent rheumatologists and transplant physicians, informed consent, and approval by the ethical committee were part of the protocol of Tyndall et al. [29]

High-Dose Chemotherapy and PBSC Infusion

The PBSC mobilization regimen consisted of Cyclophosphamide 4.0 g/m2 IV infusion over 6 hours on day 1, along with Mesna (first 3.0 g/m2 IV, then 500 mg every 3 hours orally/IV for eight doses). On day 7 after completion of the Cyclophosphamide, patients began subcutaneous injections of recombinant human G-CSF (Neupogen, Granocyte, Leukostim) 10 mg/kg/d. On recovery of neutrophils to a level greater than 1.2x109/l (usually 12 to 15 days after Cyclophosphamide treatment), patients underwent a leukapheresis procedure using AS TEC 204 (Fresenius, Germany) or Spectra LRS 07 (COBE, Lakewood, CO) apheresis equipment. Cells were cryopreserved using a controlled-rate liquid nitrogen freezer using previously published methods [10]. After PBSC procurement, high-dose chemotherapy with BEAM (BCNU 300 mg/m2 on day -7, Etoposid 800 mg/m2 and Ara-C 800 mg/m2 on days -6, -5, -4, -3, Melphalan 120 mg/m2 on day -2) for NHL and HD patients, Alceran (200 mg/m2 on day -2) for patients with AL, Cy (200-140 mg/kg in divided doses for 4 days -6, -5, -4, -3 with/or not ATG (total doses 60 mg/kg) for patients who suffered from SLE were administered. PBSCs were thawed and infused 24 hours after the completion of high-dose chemotherapy.

Phenotypic analysis of mobilized cells (expression of CD 34 and CD45) was performed using multicolor flow cytometry (FACSCalibur, Becton Dickinson). Moreover, cancer cell contamination of every PBSC specimen was excluded by the use of cytological analysis.

Supportive Care

Before, during, and for 24 hours after treatment with high dose Cyclophosphamide, patients received hyperhydration with forced diuresis and Urometexan (Mesna) infusion for the prevention of hemorrhagic cystitis. Patients were treated in a single room without air filtration. All patients followed a standardized supportive care protocol including antiemetic therapy, analgesia for mucositis, transfusion support, and venoocclusive disease prophylaxis. A low microbial diet, oral daily Fluoroquinolone (1 g/d) changed to intravenous Cefepime on neutropenic fever, Fluconazole (400 mg/d) and Acyclovir (10 mg/kg/d) and aerosolized Amphotericin B (10 mg twice daily) were started upon admission and discontinued when the ANC rebounded to 0.5x109/l. Platelets irradiated with 25 Gy and red blood cells were given to maintain a platelet count greater than 20 000/μl and a hemoglobin level greater than 8.0 g/dl. For the first 6 months after transplantation, patients were treated orally with daily oral Fluconazole and Trimethoprim/Sulfamethoxazole three times a week.

Harvesting and Ex Vivo MSC Culture

A median of 50 ml of bone marrow aspirate was obtained under sterile conditions by puncture of posterior iliac crests of patients or donors (n=9) under local anesthesia during standard pre-transplant staging approximately 2 days before high-dose Cyclophosphamide mobilization and 30 days before scheduled PBSC infusion. Washed heparinized bone marrow cells were re-suspended in phosphate-buffered solution (PBS, Sigma-Aldrich, Germany) and overlaid on Ficoll density gradient (1.078 g/l), then centrifuged for 20 min at 1000 g. A median of 320x106 (range 250–600 x106) mononuclear cells (MNC) were collected from the interface, washed three times in PBS, and re-suspended in α-modified minimum essential medium (αMEM, Sigma-Aldrich, Germany) containing 100 μg/ml gentamycin and 5% human platelet lysate (PL). After the cell number was counted, 30 ml of cell suspension was plated in a 175 cm2 plastic culture flask (Nunc, Denmark).

It is important to note that for clinical use with a therapeutic intent we used 5% platelet lysate to replace fetal calf serum (FCS) in the MSC culture. Platelet lysate was obtained from several allogeneic platelet units prepared by machine trombocytaphereis using AS TEC 204 (Fresenius, Germany). The platelet units were frozen at -40 C, thawed, mixed, aliquoted and lysate frozen at -20 C until use.

MSCs were cultured in humidified incubators with 5% CO2 and initially allowed to adhere for 72 hours, followed by a media change every 3 days. When cultures reached more than 90% confluence, adherent cells were detached with 0.05% trypsin-EDTA (Sigma-Aldrich, Germany) and replated at a density of 0.8x106 per 175 cm2 flask until processing for cryopreservation. Harvested MSCs from 1-2 passages were cryopreserved with a rate-controlled freezer (Planer Kryo 560-16) in 10% human Albumin solution (Microgen, Russia) and in a final concentration of 10% Dimethylsulfoxide (Sigma-Aldrich, Germany) and 10% Hydroxyethylstarch in freezing bags. 

Cell cultures were tested for sterility weekly and before cryopreservation (Municipal Hospitals N1, Microbiology Laboratory, Novosibirsk) for the presence of bacterial/fungal contamination via microbiological cultural tests. All cell manipulations were performed in a sterile class II biological safety cabinet.

The number of MSCs was estimated by the quantity of colony forming unit-fibroblasts (CFU-F). For that, 106 of bone marrow MNCs were cultivated in Petri dishes for 14 days and stained using Giemsa protocol, then the number of spindle-shaped cell colonies consisting of more than 50 cells were counted.

Flow Cytometry

Phenotypic analysis of MSCs (expression of CD3, CD14, CD16, CD20, CD34, CD73, CD90, CD105 and HLA-DR molecules) was performed using multicolor flow cytometry (FACSCalibur, Becton Dickinson). Cells were detached with 0.05% trypsin-EDTA (Sigma, USA), washed with PBS plus 2% bovine albumin, fixed in 1% paraformaldehyde, blocked with 10% normal goat serum, and incubated separately with appropriate primary antibodies (BD Bioscience, USA). Non-treated MSCs were used as negative control.

The immunosuppressive properties of MSCs

To study MSC effects on immune cell function, MSCs were first cultivated for 24 h in flat-bottomed 96-well or 24-well plates in α-MEM/20% fetal calf serum (FCS, Gibco, USA). After this, peripheral blood MNCs (PBMNCs) from donors were added to MSC monolayer and stimulated with mitogens or alloantigens (mixed lymphocyte culture, MLC). For MLC, 0.1x106 PBMNCs from two donors were cultivated for 5 days in RPMI-1640 medium supplemented with 0.3 mg/ml L-glutamine, 100 μg/ml Gentamycine and 10% of heat-inactivated donor AB (IV) serum. Mitogen-induced proliferative response was studied in 3-day cultures of donor PBMNCs, which were activated by Concanavalin A (ConA, 15 μg/ml, Sigma-Aldrich, Germany) or 1 μg/ml monoclonal antibodies against CD3 (anti-CD3, Becton Dickinson, USA). Cell proliferation was measured by incorporation of 3H-thymidine that was added at 1 μCi/well during  the last 18 h of cultivation. Proliferative response of MNCs cultivated without MSCs was used as control.

Support for hematopoiesis by MSC (CFU Assay)

To estimate MSCs' effect on colony-forming activity of hematopoietic progenitor cells, bone marrow MNC were grown in “complete” methylcellulose medium (Methocult H4344, Stem Cell Technologies, Vancouver, BC), containing hSCF, hGM-CSF, hIL-3, and hEPO at a density of 25x105/ml. Autologous MSC were added to MNCs in MNC: MSC ratios of 1:1 and 10:1 in triplicates. Cultures were grown at 37°C, 5% CO2 for 14 days, then the numbers of erythroid- and granulocyte-macrophage colony-forming units (CFU-E and CFU-GM, respectively) were calculated. Colonies were considered if consisted of at least 50 cells.

MSC Infusion

On the day of infusion, cryopreserved units were thawed ex tempore in a 37°C water bath, washed twice with PBS, transferred into 60-ml syringes with 10% human Albumin and infused into patients one hour after the PBSC infusion through a side port of a running 0.9% saline IV infusion into a central catheter over 10 to 20 minutes. Patients were premedicated with Acetaminophen (650 mg) and Diphenhydramine. Vital and clinical signs and symptoms were monitored at the time of infusion and every 15 minutes thereafter for 3 hours, followed by every 2 hours for 6 hours and every 8 hours for 3 days. There was no immediate or delayed toxicity related to MSC infusion. None of the patients experienced allergic reactions or respiratory symptoms.

Statistical analysis

Statistica 6.0 software for Windows, StatSoft Inc. USA was used for basic descriptive, and correlation analysis of data. The statistical significance was assessed with the Mann-Whitney U-test. The T-test was used to analyze the difference in means when comparing two groups. In assessing correlation, we used 2D scatterplots estimated correlation coefficient r and P-value for Rank Order Correlation Spearmen test. A p-value of less than 0.05 was considered statistically significant.

Results

MSC characteristics

At the first stage we compared the quantity of MSCs in bone marrow of patients with hemoblastosis and healthy donors. Since MSCs were first described as fibroblast-like cells capable of forming colonies 13], the initial content of MSC precursors among bone marrow MNCs was measured as a colony-forming unit fibroblast (CFU-F) number. The mean number of CFU-F in the control group was 36±3 colonies per 106 bone marrow-derived MNCs (min-max range 16–70). The CFU-F number in patients with hemoblastosis was 21±3 (p<0.05). The range of values in the patient group widely varied (from 1 to 67 CFU-F), and 70% of samples showed CFU-F numbers that were below the lower quartile value of control group (<25 CFU-F). The most significant decrease of CFU-F number was revealed in patients with NHL (16±5, p<0.01). In patients with MM and HL number of MSC precursors was also decreased (19±10 and 26±7, respectively; p>0.05). Decreasing CFU-F numbers mean that MSC progenitors in bone marrow of investigated patients are present at a lower amount.

Taking into consideration the MSC deficiency in patients with hemoblastosis, it seemed important to evaluate their ability for expansion in vitro. With that aim we analyzed the growth rate of MSC by measuring cultivation time until confluence. In healthy volunteers, confluent growth in MSC cultures was reached by day 15±0.5 (range 11–22 days). Meanwhile, in the patient group 80–90% confluence took on average 26±2 days (range 10–50); 23±3 days in patients with HL (p<0.01); 29±3.5 days in patients with NHL (p< 0.01), and 30±4 days in patients with MM (p<0.01). It seems to be important that despite a low CFU-F number in patient cultures it was possible to isolate and in vitro expand MSCs from patients with hematological malignancies.

MSC immunophenotype

Further, we characterized the immunophenotype of MSCs. Classically, MSCs are defined as cells expressing STRO-1, CD105 (SH2), CD71, CD73 (SH3, SH4), CD90 (Thy1) surface markers and not expressing lineage (CD3, CD14, CD20, CD16) and hematopoietic (CD34, CD45) markers along with HLA-DR antigen [11, 30]. We observed that on the first passage the MSCs of healthy volunteers expressed  CD73 (88±3.7%), CD90 (83±2.6%) and CD105 (90±6.3%), while only some few MSCs expressed CD34 (0.7±0.3%), CD3 (3.9±1.5%), CD20 (5.3±2.3%), CD16 (5.6±1.7%), CD14 (5.6±2.3%), and HLA-DR (11.1±1.6%).

The MSCs of patients with ALL, HL, NHL and MM were found to express a similar immunophenotype. However, several differences were revealed as well. Firstly, CD73, CD90 and CD105-positive cells were lowered (78±6.8, 71±8.7 and 82±10% correspondingly; p>0.05). Secondly, in contrast to healthy volunteers, MSCs of patients with hemoblastosis showed a two-fold increased number of HLA-DR-positive cells (23±4.8 vs 11.1±1.6%, p<0.05), which is in agreement with published data [6].

Immunosuppressive properties of MSCs

Evaluation of the immunosuppressive activity of MSCs showed that donor MSCs rendered a dose-dependent suppressive effect on T-cell proliferation in mixed lymphocyte cultures (Fig. 1) as well as in cultures stimulated with ConA or monoclonal anti-CD3 antibodies (data not shown). The most pronounced effect was observed at the MSC:MNC ratio of 1:1. However, even at lower concentrations of MSCs (MSC:MNC ratio of 1:2 and 1:4) their suppressive activity remained high, and averaged 44–47%. In patients with hemoblastosis a significant suppressive effect of MSCs was registered only at the highest concentration of MSCs in culture (MSC:MNC ratio of 1:1). Nevertheless, even in this case the level of immunosuppressive activity of patient MSCs was lower compared to the level in control group (52±7 and 72±18%, correspondingly; p>0.05), varying from 18 to 64%. Reduction of MSC dose in mixed lymphocyte cultures strongly decreased ability of MSCs to block T-cell proliferative response.

2009-4-en-Sergeevicheva-et-al-Figure-1.JPG

Figure 1. Effects of donor and patient MSCs on proliferative response of T-cells in MLC.
MNCs from two donors (both 0.1x106 per well) have been cultivated for 5 days in the absence (control) or presence of MSCs of healthy donors (n=7) or hematologic patients (n=10). Cellular uptake of 3H-thymidine added at 18 hours before the end of cultivation was used to measure cell proliferation rate. Results are expressed as a suppression rate in percents calculated using the following formula: Sergeevicheva-fig1-formula.jpg, where cpmMNC+MSC is proliferation rate of MNCs in presence of MSCs, and cpmMNC is proliferation rate of MNCs in absence of MSCs (control).

Support of hematopoiesis by MSC

One of the promising fields of therapeutic application of MSCs is their use for the rapid recovery of hematopoiesis after bone marrow transplantations. This statement is based on the ability of mesenchymal cells to support the hematopoietic progenitors [9, 15]. However, the question about the integrity of hematopoiesis-supporting potential of MSCs in case of hemoblastosis still remains open. Assessment of the colony-forming potential of patient bone marrow MNCs under co-incubation with autologous MSCs showed that the presence of MSCs (in ratio of 1:1) increased the number of CFU-E and CFU-GM approximately five times (Fig. 2). It should be noted that even in the presence of lower MSC concentration (in ratio of 1:10) a two-fold increase of hematopoietic colonies was also registered. The ability of MSCs to support hematopoietic progenitors in vitro was observed in all investigated cases (ALL, n=3; HL, n=3; NHL, n=3).

2009-4-en-Sergeevicheva-et-al-Figure-2a.JPG

Figures 2a/b. Effects of MSCs on colony-forming activity of bone marrow MNCs.
Bone marrow MNCs of hematologic patients (n=9) were cultivated for 14 days in absence (control) or presence of autologous MSC at various concentrations (1:1 and 1:10) in semi-liquid methylcellulose medium. At the end of cultivation the amounts of erythroid (A) and granulocyte-macrophage (B) colonies per 105 MNCs were calculated.    * - pU < 0,05 and ** - pU < 0,01 – versus control; Mann-Whitney U-test.


2009-4-en-Sergeevicheva-et-al-Figure-2b.JPG

Hematopoietic engraftment and clinical outcome

Patients of both groups received a PBSC infusion containing equal doses of CD34+cells: the mean number of CD34+ mononuclear cells was 5.57х106/kg in the control group and 5.64х106/kg in the group with MSC co-transplantation. The dose of mesenchymal cells infused varied from 0.8x106 to 23x106 (mean 6.64x106).

2009-4-en-Sergeevicheva-et-al-Figure-3.JPG

Figure 3. Effects of MSCs infusions on neutrophil recovery. The t-test was used to evaluate a difference in period of neutrophil recovery.


2009-4-en-Sergeevicheva-et-al-Figure-4.JPG

Figure 4. Effects of MSCs infusions on neutrophil recovery. The t-test was used to evaluate a difference in period of platelets recovery.

There was no significant correlation between the number of MSCs and days of neutropenia or thrombocytopenia. However, we found a significant invert correlation between the number of MSCs and days of neutropenia in selected group, when infused PBSC were <3.0x106/kg.

No differences in analysis of severity and rate of complication, transfusion dependence, total or disease-free survival between the groups compared were revealed. Patients underwent standard restaging evaluation with computed tomography 42 days after transplantation and every 3 months thereafter. All patients evaluated on Day +60 were free of symptoms and clinical findings. Median follow-up of the patients is 9 months (range 4 to 22 months). Four patients died as a result of early disease progression (NHL, n= 2; HD, n=1; MM, n=1). All of them had refractory disease before PBSC transplantation. Of the 34 remaining patients, 33 are without evidence of disease; one has a stable disease (plato-phase in MM).

Transplant-related mortality / Toxicity

Two patients died on Day +7 and +21 due to transplant-related complications. There was one patient who died before engraftment. The cause of death in patient 1 on Day +7 was pneumonia and Candida sepsis as background. Patient 2 recovered hematopoiesis on Day +11, but died from pneumonia on Day +21. Progression of HD: lymphoadenopathy in the mediastinum was also revealed on autopsy of patient 2. Similar toxicity and causes of death were found in the control group: 3 fatal outcomes due to infection among 42 transplanted patients.

Discussion

The work presented here originated from the question of whether MSCs isolated from bone marrow of patients with hematologic malignancies possess intact functional properties including immunosuppressive activity and hematopoiesis-supporting ability. The transplantation of autologous bone marrow is widely used in clinical practice, but very little data exists on the characteristics of MSCs from the bone marrow of these patients, and the reported results often differ from one other.

Some authors have shown a statistically significant decrease of CFU-F numbers in cases of acute myeloid leukemia either in primary patients and patients after PCT courses [5, 6, 8] or for patients suffering from lymphomas, acute lymphoid leukemia and multiple myeloma [6, 23]. Notable is that the CFU-F number in patients varies from total absence to donor values. Moreover, neither sex nor age or involvement of bone marrow or time of the last PCT course affects the number of CFU-F [23]. In this study we also found a decrease in the CFU-F numbers for bone marrow samples obtained from patients with hemoblastosis. However, despite a low CFU-F number in patients our data display the principal possibility of isolation and in vitro expansion of MSC from patients with hematological malignancies.

Moreover, our results demonstrated a decrease in the proliferative capacity of in vitro expanded patient MSCs. For achieving confluence growth of patients’ MSCs, cultivation time needed to be twice as long. On the one hand, this may be caused by inhibition of proliferative potential in the patients’ MSCs, and on the other hand it may be caused by initially lowered content of MSC in bone marrow MNCs under hematological malignancies.

Our data shows that the MSCs of patients with ALL, HL, NHL, and MM do not express linear and hematopoietic antigens but are positive for some “stromal” markers. Along with that we managed to elicit some other special features. Namely, in the MSC population there was a lower number of CD73, CD90, and CD105-positive cells. Moreover, patient MSCs exhibited a two-fold increased number of HLA-DR-positive cells. Our data corresponds with Campioni D. et al [6], who used 4-color flow cytometry to show significant decreases in CD73, CD90, and CD105 expression on MSCs of 43 hematological patients. We have found this fact just as a tendency but this probably was caused by small array of patients (n=16) or by using 1-2-color flow cytometry.

We further found that in contrast to donor cells, patient MSCs in some cases did not suppress but even increased a proliferative response in MLC (data not shown), which corresponds with published data [17]. The low number of such observations did not allow us to connect this feature either with a distinct nosologic form of hemoblastosis, nor with particular phenotype or morphology of MSCs. One of the possible reasons for this phenomenon could be the ability of MSCs to secrete IL-7, which induces and supports lymphocyte proliferation [9].
 
Finally, in all investigated cultures (ALL, HL, NHL) we observed the ability of MSCs to support growth of hematopoietic progenitors in vitro. Published data concerning this issue can not be called univocal. For example, it was demonstated that the stromal cells of patients with acute myeloid leukemia possessed a low potential to stimulate growth of allogeneic hematopoietic precursors [8]. Meanwhile Mayani et al. [19] have shown that stromal cells of patients with AML display intact hematopoiesis-supporting activity, which strongly depends on the presence of CFU-F.

Summarizing the given experimental data we can conclude that MSCs of patients with hemoblastosis used in our study correspond to the Minimal criteria for defining multipotent mesenchymal stromal cells settled in the International Society for Cellular Therapy position statement [11]. These cells are characterized by adhesiveness, show fibroblast-like morphology, and a specific phenotype. Moreover, patients' MSCs display immunosuppressive and hematopoiesis-supporting activity. However, they have a number of distinct features. For instance, patient stromal cells in comparison with healthy donor cells contain lower numbers of CD73, CD90, and CD105-positive cells and a two-fold increased number of HLA-DR-positive cells. In addition, MSCs in hemoblastosis display lower levels of suppressive activity that is only become apparent at high concentrations of MSCs. It is important to note that described features of MSCs in hemoblastosis are not crucial for their hematopoiesis-supporting activity. This fact in combination with the ability of MSCs to expand ex vivo represents the basis for the clinical application of hematopoietic stem cell co-transplantation with mesenchymal stromal cells in oncohematology for the acceleration of hematopoiesis recovery.

Based on our clinical findings, we propose that culture-expanded autologous MSCs can be used to improve the rate and quality of hematopoietic engraftment, particularly in patients who previously received stroma-damaging therapy. Indeed, our report demonstrates that autologous MSCs can be successfully culture-expanded in FCS-free conditioning media, and infused IV for therapeutic intent with efficacy and without toxicity into different nosologic groups of patients at the time of PBSC transplantation. We have optimized MSC culture expansion methods to generate optimal numbers of autologous MSCs in a relatively short period of time for clinical use with a therapeutic intent without xenogenic components (e.g., FCS) [7].

Patients treated with high-dose chemotherapy generally experience complete and rapid neutrophil and platelet engraftment when supported with mobilized PBSCs containing >2–3 106 CD34+ cells. On the other hand, patients receiving lower doses of CD34+ cells are at increased risk for delayed platelet engraftment [3, 2].

Unsuccessful mobilization of CD34+ cells is commonly associated with extensive previous therapy, which is also associated with microenvironment damage. Coupled with low doses of CD34+ cells, an abnormal marrow microenvironment increases the risk of delayed engraftment. Sequential use of high-dose chemotherapy is also toxic to the marrow microenvironment, as evidenced by the delayed hematopoietic recovery after transplantation despite infusion of equal numbers of stem cells [12, 20, 22, 25]. Therefore, attempts to protect and improve the bone marrow microenvironment ex vivo are likely to better hematopoiesis engraftment after suboptimal СD34+ transplantation.

In conclusion our results indicate that the proposed cellular therapy protocol is feasible and may have a number of beneficial clinical effects in the setting of hematopoietic stem-cell transplantation. We therefore suppose studying it in more depths in randomized trials.

References

1. Aggarwal S., Pittenger M.F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-1822.

2. Akard L. Optimum methods to mobilize stem cells. J Clin Oncol 2000; 18: 3063.

3. Appelbaum F. The current status of hematopoietic cell transplantation. Annu Rev Med 2003; 54: 491.

4. Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, et al. Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford) 2007; 46:403-408.

5. Campioni D, Lanza F, Moretti S, Dominici M, Punturieri M, Pauli1 S et al. Functional and immunophenotypic characteristics of isolated CD105(+) and fibroblast(+) stromal cells from AML: implications for their plasticity along endothelial lineage. Cytotherapy 2003; 5: 66-79.

6. Campioni D, Moretti S, Ferrari L, Punturieri M, Castoldi GL, Lanza F. Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment. Haematologica 2006; 91:364-368.

7. Capelli C, Domenghini M, Borleri G, Bellavita P, Poma R, Introna M et al. Human platelet lysate allows expansion and clinical grade production of mesenchymal stromal cells from small samples of bone marrow aspirates or marrow filter washouts. Bone Marrow Transplantation 2007; 1–7.

8. Carlo-Stella C, Tabilio A, Regazzi E, Garau D, La Tagliata R, Trasarti S, et al. Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors. Bone Marrow Transplant 1997; 20:465-71.

9. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2000; 28:875-884.

10. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838-3843.

11. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-317.

12. Fried W, Kedo A, Barone J: Effects of cyclophosphamide and of busulfan on spleen colony-forming units and on hematopoietic stroma. Cancer Res 1977; 37:1205-1209.

13. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17:331-340.

14. Gupta P, Blazar BR, Gupta K, Verfaillie CM. Human CD34(+) bone marrow cells regulate stromal production of IL-6 and G-CSF and increase the colony-stimulating activity of stroma. Blood 1998; 91:3724-33.

15. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000; 18:307-316.

16. Le Blanc K , Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439-1441.

17. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003; 57:11-20.

18. Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003; 10:228-241.

19. Mayani H., Guilbert LJ, Janowska-Wieczorek A. Functional characterization of fibroblastic cells in long-term marrow cultures from patients with acute myelogenous leukemia. Leukemia 1993; 7:1564-1569.

20. McManus PM, Weiss L: Busulfan-induced chronic bone marrow failure: Changes in cortical bone, marrow stromal cells, and adherent cell colonies. Blood 1984; 64:1036-1041.

21. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103:4619-4621.

22. Migliaccio A, Migliaccio G, Johnson G, et al: Comparative analysis of hematopoietic growth factor released by stromal cells from normal donors or transplant patients. Blood 1990; 75:305-312.

23. Mueller LP, Luetzkendorf J, Mueller T, Reichelt T, Simon H Schmoll HJ. Presence of mesenchymal stem cells in human bone marrow after exposure to chemotherapy: evidence of resistance to apoptosis induction. Stem Cells 2006; 24:2753-2765.

24. Muguruma Y, Yahata T, Miyatake H, Sato T, Uno T, Itoh J et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood 2006; 107:1878-1887.

25. O’Flaherty E, Sparrow R, Szer J: Bone marrow stromal function from patients after bone marrow transplantation. Bone Marrow Transplant 1995; 15:207-212.

26. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143-147.

27. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T et al.  Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007; 109:228-234.

28. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 2002; 20:530-541.

29. Tyndall A, Fassas A, Passweg J, Ruiz de Elvira C, Attal M, et al.: Autologous haematopoietic stem cell transplants for autoimmune disease — feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and theInternational Stem Cell Project for Autoimmune Disease. Bone Marrow Transplant 1999; 24:729-734.

30. Ucelli A., Moretta L., Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol. 2006; 36:2566-73.

31. Zhang W, Ge W, Li C, You S, Liao L, Han Q et al. Effects of mesenchymal stem cells on differentiation, maturation and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004; 13:263-71.

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К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. 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В.<sup>1</sup>, Шевела Е. Я.<sup>1</sup>, Сизикова С. А.<sup>1</sup>, Кулагин А. Д.<sup>2</sup>, Крючкова И. В.<sup>1</sup>, Гилевич А. В.<sup>1</sup>, Лисуков И. А.<sup>2</sup>, <br>Козлов В. А.<sup>1</sup>, Останин А. А.<sup>1</sup>, Черных Е .Р.<sup>1</sup></p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(377) "

Сергеевичева В. В.1, Шевела Е. Я.1, Сизикова С. А.1, Кулагин А. Д.2, Крючкова И. В.1, Гилевич А. В.1, Лисуков И. А.2,
Козлов В. А.1, Останин А. А.1, Черных Е .Р.1

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1Институт клинической иммунологии СО РАМН, Новосибирск, Россия
2Новосибирский государственный медицинский университет, Новосибирск, Россия

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Мезенхимальные стромальные клетки (МСК), выделенные из костного мозга, обладают иммунорегуляторной активностью и способны поддерживать гемопоэз. К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. Сокращение периода восстановления кроветворения свидетельствует  о позитивном влиянии МСК на гемопоэз.

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Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

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1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia

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Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.

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Sergeevicheva<sup>1</sup>, Ekaterina Y. Shevela<sup>1</sup>, Svetlana A. Sizikova<sup>1</sup>, Alexander D. Kulagin<sup>2</sup>, Irina V. Kruchkova<sup>1</sup>, <br>Andrey V. Gilevich<sup>1</sup>, Igor A. Lisukov<sup>2</sup>, Vladimir A. Kozlov<sup>1</sup>, Alexander A. Ostanin<sup>1</sup>, Elena R. Chernykh<sup>1</sup></p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(336) "

Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

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Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

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Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.

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Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.

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1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia

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1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia

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Козлов В. А.1, Останин А. А.1, Черных Е .Р.1

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К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. Сокращение периода восстановления кроветворения свидетельствует  о позитивном влиянии МСК на гемопоэз.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2735) "

Мезенхимальные стромальные клетки (МСК), выделенные из костного мозга, обладают иммунорегуляторной активностью и способны поддерживать гемопоэз. К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. Сокращение периода восстановления кроветворения свидетельствует  о позитивном влиянии МСК на гемопоэз.

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Мезенхимальные стромальные клетки (МСК), выделенные из костного мозга, обладают иммунорегуляторной активностью и способны поддерживать гемопоэз. К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. Сокращение периода восстановления кроветворения свидетельствует  о позитивном влиянии МСК на гемопоэз.

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1Институт клинической иммунологии СО РАМН, Новосибирск, Россия
2Новосибирский государственный медицинский университет, Новосибирск, Россия

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1Институт клинической иммунологии СО РАМН, Новосибирск, Россия
2Новосибирский государственный медицинский университет, Новосибирск, Россия

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Video description

Human mesenchymal stromal cells (hMSCs) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. Although a unique marker for prospective isolation of hMSC is still lacking, they can be easily isolated by plastic adherence from bone marrow and other tissues. Furthermore, hMSCs are capable of expanding in vitro as undifferentiated cells [1]. In vitro, human MSCs are heterogeneous in that they contain morphologically distinct kinds of cells: spindle-shaped and large cuboidal or flattened cells. Colter et al. described an additional population of small and rounded cells with rapidly self-renewing capacity [2].

Some therapeutic approaches have demonstrated the ability of MSCs to regenerate injured tissues [3, 4]. Transplantation experiments in mice and primates have shown that intravenously administered MSCs distribute to several tissues. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. This migration ability is highly dependent on the flexibility of the cell. For example, basic fibroblast growth factor (bFGF) applied in vitro has been shown to influence not only an attraction but also routing of MSCs by manipulating the orientation of the cytoskeleton. Basic FGF attracted the MSCs by directly influencing the migratory ability through a parallel-orientation of the cells' actin filament [5]. In contrast, the inhibition of the FGF pathway indirectly might cause differentiation [6].

Recently, several factors have been identified which mediate homing and migration of MSCs to injured tissues. For example, ischemia-reperfusion-induced acute kidney injury leads to an increase of the stroma-derived factor 1 (SDF-1) expression in the kidney. At the same time, SDF-1 expression decreases in the bone marrow, thereby reversing the normal gradient between bone marrow and the periphery, and thus mediating homing to the injured tissue and migration of MSCs expressing SDF-1 receptor CXCR4 [7]. Additionally, MSCs were strongly attracted by hepatocyte growth factor (HGF) gradients as well, and proved their chemo-invasiveness across a reconstituted basement membrane in vitro [8]. These results suggest that the SDF-1-CXCR4 and HGF-c-met axes may be involved in recruitment of expanded MSCs for damaged tissues. Finally, the investigation of the traversal mechanism by which MSCs migrate into injured tissues revealed that both P-selectin and VCAM-1 are equally required for this process. Here, MSCs were able to roll and adhere to post-capillary venules in vivo showing similar migratory behaviour to leukocytes [9].

The presented videos show the proliferation of hMSC kept in DMEM-low glucose with fetal calf serum as described (1). Pictures were taken in the phase-contrast mode every 15 min for a time period of 2 days from cultures incubated on an Olympus IX81 microscope equipped with incubation chamber and SIS software. In video 1, on the right picture's edge, a large flattened cell remains almost stationary for the complete recording time. It communicates, “pulsing” with neighbouring cells by extending protrusions forming filopodiae/lobopodiae/lamellopodiae, coming close together or only contacting slightly at the surface. In this cell, the floating changes of the cell body are visible, combined with changes of the nucleus location. The cytoplasmic changes suggest an active orientation of actin-fibers, visible as dark lines directed to the outer borders of the cell. The high count of actin-fibers is particularly characteristic for cells that are not undergoing any more cell division but possibly serving as “nursery” cells. The actin fibers can regularly be observed in old and stressed cultures of hMSC as well (Fig.1). 

2010_Lange_Figure1.png

Figure 1. hMSC culture after prolonged propagation. Ageing cultures show a majority of flattened cells with actin fibres along the cell body. No small and round cells are visible, suggesting a stationary phase of this culture.

Departing cells might leave behind molecular signatures in form of extra-cellular matrices seen as dark-gray lines without any cell body. These traces often are “visited” by trampers, sometimes taking up particles of the traces, sometimes "sniffing" only and continuing on their way. The vagabonds easily might travel more than 500 µm, themselves being only a few µm in size. The length of other cells might reach 300‒600 µm (see upper quarter, video 1), with a width of only ca. 5 µm. During the travel, cells might condense, forming small and round, only loosely adherent cells (see lower quarter, Video 1).


Video 1.

This is the moment when cells prepare for division. The cell divisions itself takes roughly 15‒20 min, and afterwards the new 2 daughter cells either continue to travel as long stretched or short cells or stay in place and provide contact and information to other arriving cells. It is known that MSCs itself express SDF-1 and HGF. Although we do not show stainings for these factors, they might be one part of the interaction of MSCs seen in vitro.

In video 2, the initial cell number was higher, the pictures taken every 10 min for a time period of 2 days, and the cell body shown in semi-3D-dimensionality. Here, the video shows the active interaction of MSCs.

Video 2.

The observer has the impression of witnessing a highly communicative community where the members have a lively exchange experience. The movements of MSCs are accompanied by 1. change of cell shape, 2. polymerisation of cellular actin, 3. formation of lamellopodiae at the leading edge, 4. concentration of the main cell body on the leading edge, and 5. movement of the whole cell body via 6. formation of uropodiae at the lateral edge. The whole process of the MSCs' proliferation and movement observed in vitro is similar to that described for leukocytes during the process of homing to inflamed tissues. Thus, our results support the notion of similar behaviour of MSCs and leukocytes.

 However, the high motility of MSCs in vitro also suggests that cloning with cloning rings even at low density of 1‒5 cells/cm2 might not lead to the pure clonal populations clearly derived from 1 cell only. Single travellers easily might contaminate colonies. Therefore, we suggest a more rigid cloning technique either by seeding a limited number of mononuclear cells (MNCs), supposed that the MSC frequency in MNCs is 1/104‒105 or by rigid cloning of 0.3 cells/well and regular observation of the forming clones.

Acknowledgements

This work was supported by the Federal Ministry of Education and Research Germany; Contract grant number: 13N8904 (HyCelex). We thank B. Brunswig-Spickenheier for critical reading of the manuscript.

References

1. Lange C, Cakiroglu F, Spiess AN, Cappallo-Obermann H, Dierlamm J, Zander AR. Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol. 2007;213(1):18-26.

2. Colter DC, Sekiya I, Prockop DJ. Identification of a subpopulation of and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci U S A. 2001;98(14):7841-5.

3. Lange C, Tögel F, Ittrich H, Clayton F, Nolte-Ernsting C, Zander AR, Westenfelder C. Administered mesenchymal stem cells are renoprotective in ischemia/reperfusion acute renal failures in rats. Kidney Int. 2005;68(4):1613-7.

4. Tögel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005;289(1):F31-42.

5. Schmidt A, Ladage D, Schinköthe T, Klausmann U, Ulrichs C, Klinz FJ, Brixius K, Arnhold S, Desai B, Mehlhorn U, Schwinger RH, Staib P, Addicks K, Bloch W. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells. 2006;24(7):1750-8.

6. Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K, Werbowetski-Ogilvie T, Ramos-Mejia V, Rouleau A, Yang J, Bossé M, Lajoie G, Bhatia M. IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature. 2007;448(7157):1015-21.

7. Tögel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005;67(5):1772-84.

8. Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells. 2006;24(5):1254-64.

9. Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood. 2006;108(12):3938-44.

" ["~DETAIL_TEXT"]=> string(11951) "

Video description

Human mesenchymal stromal cells (hMSCs) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. Although a unique marker for prospective isolation of hMSC is still lacking, they can be easily isolated by plastic adherence from bone marrow and other tissues. Furthermore, hMSCs are capable of expanding in vitro as undifferentiated cells [1]. In vitro, human MSCs are heterogeneous in that they contain morphologically distinct kinds of cells: spindle-shaped and large cuboidal or flattened cells. Colter et al. described an additional population of small and rounded cells with rapidly self-renewing capacity [2].

Some therapeutic approaches have demonstrated the ability of MSCs to regenerate injured tissues [3, 4]. Transplantation experiments in mice and primates have shown that intravenously administered MSCs distribute to several tissues. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. This migration ability is highly dependent on the flexibility of the cell. For example, basic fibroblast growth factor (bFGF) applied in vitro has been shown to influence not only an attraction but also routing of MSCs by manipulating the orientation of the cytoskeleton. Basic FGF attracted the MSCs by directly influencing the migratory ability through a parallel-orientation of the cells' actin filament [5]. In contrast, the inhibition of the FGF pathway indirectly might cause differentiation [6].

Recently, several factors have been identified which mediate homing and migration of MSCs to injured tissues. For example, ischemia-reperfusion-induced acute kidney injury leads to an increase of the stroma-derived factor 1 (SDF-1) expression in the kidney. At the same time, SDF-1 expression decreases in the bone marrow, thereby reversing the normal gradient between bone marrow and the periphery, and thus mediating homing to the injured tissue and migration of MSCs expressing SDF-1 receptor CXCR4 [7]. Additionally, MSCs were strongly attracted by hepatocyte growth factor (HGF) gradients as well, and proved their chemo-invasiveness across a reconstituted basement membrane in vitro [8]. These results suggest that the SDF-1-CXCR4 and HGF-c-met axes may be involved in recruitment of expanded MSCs for damaged tissues. Finally, the investigation of the traversal mechanism by which MSCs migrate into injured tissues revealed that both P-selectin and VCAM-1 are equally required for this process. Here, MSCs were able to roll and adhere to post-capillary venules in vivo showing similar migratory behaviour to leukocytes [9].

The presented videos show the proliferation of hMSC kept in DMEM-low glucose with fetal calf serum as described (1). Pictures were taken in the phase-contrast mode every 15 min for a time period of 2 days from cultures incubated on an Olympus IX81 microscope equipped with incubation chamber and SIS software. In video 1, on the right picture's edge, a large flattened cell remains almost stationary for the complete recording time. It communicates, “pulsing” with neighbouring cells by extending protrusions forming filopodiae/lobopodiae/lamellopodiae, coming close together or only contacting slightly at the surface. In this cell, the floating changes of the cell body are visible, combined with changes of the nucleus location. The cytoplasmic changes suggest an active orientation of actin-fibers, visible as dark lines directed to the outer borders of the cell. The high count of actin-fibers is particularly characteristic for cells that are not undergoing any more cell division but possibly serving as “nursery” cells. The actin fibers can regularly be observed in old and stressed cultures of hMSC as well (Fig.1). 

2010_Lange_Figure1.png

Figure 1. hMSC culture after prolonged propagation. Ageing cultures show a majority of flattened cells with actin fibres along the cell body. No small and round cells are visible, suggesting a stationary phase of this culture.

Departing cells might leave behind molecular signatures in form of extra-cellular matrices seen as dark-gray lines without any cell body. These traces often are “visited” by trampers, sometimes taking up particles of the traces, sometimes "sniffing" only and continuing on their way. The vagabonds easily might travel more than 500 µm, themselves being only a few µm in size. The length of other cells might reach 300‒600 µm (see upper quarter, video 1), with a width of only ca. 5 µm. During the travel, cells might condense, forming small and round, only loosely adherent cells (see lower quarter, Video 1).


Video 1.

This is the moment when cells prepare for division. The cell divisions itself takes roughly 15‒20 min, and afterwards the new 2 daughter cells either continue to travel as long stretched or short cells or stay in place and provide contact and information to other arriving cells. It is known that MSCs itself express SDF-1 and HGF. Although we do not show stainings for these factors, they might be one part of the interaction of MSCs seen in vitro.

In video 2, the initial cell number was higher, the pictures taken every 10 min for a time period of 2 days, and the cell body shown in semi-3D-dimensionality. Here, the video shows the active interaction of MSCs.

Video 2.

The observer has the impression of witnessing a highly communicative community where the members have a lively exchange experience. The movements of MSCs are accompanied by 1. change of cell shape, 2. polymerisation of cellular actin, 3. formation of lamellopodiae at the leading edge, 4. concentration of the main cell body on the leading edge, and 5. movement of the whole cell body via 6. formation of uropodiae at the lateral edge. The whole process of the MSCs' proliferation and movement observed in vitro is similar to that described for leukocytes during the process of homing to inflamed tissues. Thus, our results support the notion of similar behaviour of MSCs and leukocytes.

 However, the high motility of MSCs in vitro also suggests that cloning with cloning rings even at low density of 1‒5 cells/cm2 might not lead to the pure clonal populations clearly derived from 1 cell only. Single travellers easily might contaminate colonies. Therefore, we suggest a more rigid cloning technique either by seeding a limited number of mononuclear cells (MNCs), supposed that the MSC frequency in MNCs is 1/104‒105 or by rigid cloning of 0.3 cells/well and regular observation of the forming clones.

Acknowledgements

This work was supported by the Federal Ministry of Education and Research Germany; Contract grant number: 13N8904 (HyCelex). We thank B. Brunswig-Spickenheier for critical reading of the manuscript.

References

1. Lange C, Cakiroglu F, Spiess AN, Cappallo-Obermann H, Dierlamm J, Zander AR. Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol. 2007;213(1):18-26.

2. Colter DC, Sekiya I, Prockop DJ. Identification of a subpopulation of and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci U S A. 2001;98(14):7841-5.

3. Lange C, Tögel F, Ittrich H, Clayton F, Nolte-Ernsting C, Zander AR, Westenfelder C. Administered mesenchymal stem cells are renoprotective in ischemia/reperfusion acute renal failures in rats. Kidney Int. 2005;68(4):1613-7.

4. Tögel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005;289(1):F31-42.

5. Schmidt A, Ladage D, Schinköthe T, Klausmann U, Ulrichs C, Klinz FJ, Brixius K, Arnhold S, Desai B, Mehlhorn U, Schwinger RH, Staib P, Addicks K, Bloch W. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells. 2006;24(7):1750-8.

6. Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K, Werbowetski-Ogilvie T, Ramos-Mejia V, Rouleau A, Yang J, Bossé M, Lajoie G, Bhatia M. IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature. 2007;448(7157):1015-21.

7. Tögel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney Int. 2005;67(5):1772-84.

8. Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells. 2006;24(5):1254-64.

9. Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood. 2006;108(12):3938-44.

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Саша Ланге, Аксель Цандер, Клаудиа Ланге

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Мезенхимные стволовые клетки  человека (МСКЧ) в настоящее время интенсивно изучаются на предмет их потенциального применения в качестве средства клеточной терапии в регенеративной медицине. Их можно легко выделять, например, из костного мозга посредством залипания на пластике, и размножать in vitro. Представленные видеокадры показывают пролиферацию МСКЧ,  их взаимодействия между собой и процесс их деления.  Высокая степень подвижности МСКЧ может быть причиной возможных нарушений формирования «чистых» клонов даже при низкой плотности посева клеток.

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Sascha Lange, Axel R. Zander, Claudia Lange

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Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany

Correspondence:
Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: cllange@spam is baduke.uni-hamburg.de

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Human mesenchymal stromal cells (hMSC) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. They can be easily isolated, e.g., from bone marrow by plastic adherence, and expanded in vitro. These videos show the proliferation of hMSC, and how they interact with each other and divide. The large distances hMSC can conquer call into question the cloning carried out by low-density seeding.

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Sascha Lange, Axel R. Zander, Claudia Lange

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Sascha Lange, Axel R. Zander, Claudia Lange

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Human mesenchymal stromal cells (hMSC) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. They can be easily isolated, e.g., from bone marrow by plastic adherence, and expanded in vitro. These videos show the proliferation of hMSC, and how they interact with each other and divide. The large distances hMSC can conquer call into question the cloning carried out by low-density seeding.

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Human mesenchymal stromal cells (hMSC) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. They can be easily isolated, e.g., from bone marrow by plastic adherence, and expanded in vitro. These videos show the proliferation of hMSC, and how they interact with each other and divide. The large distances hMSC can conquer call into question the cloning carried out by low-density seeding.

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Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany

Correspondence:
Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: cllange@spam is baduke.uni-hamburg.de

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Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany

Correspondence:
Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: cllange@spam is baduke.uni-hamburg.de

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Саша Ланге, Аксель Цандер, Клаудиа Ланге

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Саша Ланге, Аксель Цандер, Клаудиа Ланге

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Мезенхимные стволовые клетки  человека (МСКЧ) в настоящее время интенсивно изучаются на предмет их потенциального применения в качестве средства клеточной терапии в регенеративной медицине. Их можно легко выделять, например, из костного мозга посредством залипания на пластике, и размножать in vitro. Представленные видеокадры показывают пролиферацию МСКЧ,  их взаимодействия между собой и процесс их деления.  Высокая степень подвижности МСКЧ может быть причиной возможных нарушений формирования «чистых» клонов даже при низкой плотности посева клеток.

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Мезенхимные стволовые клетки  человека (МСКЧ) в настоящее время интенсивно изучаются на предмет их потенциального применения в качестве средства клеточной терапии в регенеративной медицине. Их можно легко выделять, например, из костного мозга посредством залипания на пластике, и размножать in vitro. Представленные видеокадры показывают пролиферацию МСКЧ,  их взаимодействия между собой и процесс их деления.  Высокая степень подвижности МСКЧ может быть причиной возможных нарушений формирования «чистых» клонов даже при низкой плотности посева клеток.

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Supplementary material

Introduction

Flow cytometry (FCM), often referred to as Fluorescence Activated Cell Sorting (FACS) has developed into a highly sophisticated cell analysis method, which facilitates the concurrent analysis of multiple cell parameters [1]. At the same time and most surprisingly, graphical presentation of FCM data is often characterized by low-quality images.

In particular, FACSDiva software has two major drawbacks: First, even the latest version does not support generation of histogram overlays. Since histogram overlays represent a convenient way of directly comparing FCM data, this is often considered a main disadvantage of the software [2]. Secondly, FACSDiva does not allow the export of high-resolution image files of any type; neither copy/paste, nor Export Worksheet Elements result in satisfying image quality. Notably, even the new built-in Save as PDF function of FACSDiva is not able to generate high-resolution, vector-based images – instead it combines the low-resolution raster/pixel graphics in a PDF file. At the same time, FACSDiva software supports high-resolution printing of FACS plots, as can easily be seen on any printout generated with the software.

Since adequate, high-quality data presentation is an important precondition for publishing research results [3], we asked whether we could develop an easy manual for generating high-quality graphs for data obtained with FACSDiva. The basic idea of this manual is to trick FACSDiva by using its print functionality to generate a high-resolution, vector-based PDF file. Notably, conferring FACS plots into PDF files not only represents a convenient way of storing FCM data in an easy accessible format, but also allows the FACS plots to be later extracted in high-resolution quality, perfectly suitable for any kind of publication including large posters.

We here describe a Figure-improvement toolbox (Diva-Fit), which we find to be easy, fast and convenient. This toolbox facilitates the export of FACS data obtained with FACSDiva into high-resolution PDF files, the removal of unwanted quadrant labels (automatically adhered by FACSDiva) and the generation of histogram overlays. Importantly, all of the software used is distributed free of charge. It should be noted that the described strategy may also be performed by combining alternative programs to the ones used here. However, in exploring various tools we found the way described below to be the most convenient. In fact, with some experience even generation of high-resolution histogram overlays takes only a few minutes using the proposed protocol.

Material and Methods

Software tools used
Diva-Fit requires several programs to be installed on the computer. We made sure that, with the exception of FACSDiva, the required software is free of charge and can easily be obtained from Internet sources. Administrative rights are necessary to install the software. If you do not have enough rights to install software, ask your local system administrator.

The following programs have been used:

BD FACSDiva 6.1.2
Any version should work

PDFCreator 0.9.5
http://www.pdfforge.org/products/pdfcreator
This version or newer is recommended. Alternatively, other PDF printer drivers possibly already installed on the computer could be used (e.g., Adobe Acrobat comes with a PDF printer driver, the free Acrobat Reader does not). However, the method will be different.

Adobe Acrobat Reader 9.1.0
http://get.adobe.com/uk/reader/otherversions/
We recommend using this version or newer.

GIMP 2.6.4
http://www.gimp.org/downloads/
GIMP is only necessary for the creation of histogram overlays. This version or newer is recommended; however, older versions should work too. Alternatively, Adobe Photoshop could be used; the treatment is only slightly different. Not every image manipulation program offers all necessary features. GIMP is a very powerful program, but quite demanding because of its complexity.

Inkscape 0.46
http://www.inkscape.org/download/
Inkscape is only necessary for the deletion of text within plots (e.g., quadrant labels). The most recent version should be used: version 0.46 or newer. Inkscape is a vector graphics editor that is also capable of modifying the content of PDF files. The low version number (0.46) represents the ongoing development status, and not everything works perfectly yet. Nevertheless, this program has a lot of features and is quite difficult to use.

Results

Diva-Fit, a toolbox for the generation of high-resolution FCM graphs
In this result section all steps of our manual are described in a concise form. For those researchers less familiar with the software tools we used, a very detailed description including screenshots is provided in the supplementary material. Part 1 describes how to generate high-resolution dot plots and histograms. Part 2 describes how to generate histogram overlays (this is based upon Part 1). Part 3 describes how to delete text within plots, e.g., quadrant labels in dot plots (also based upon Part 1).

Part 1: How to extract high-resolution dot plots and histograms from BD’s FACSDiva

Step 1: Obtaining and processing data with FACSDiva


FCM data are obtained and processed using FACSDiva. Dependent on the required style of final data presentation, dot or histogram plots can be designed. Importantly, if a histogram overlay needs to be created, it is essential to make the histograms the same size and to set the scaling of the Y-axis to identical values. To do so, mark both histograms and click the button Make Same Size. Then go to the Inspector (View --> Inspector) and at the Histogram tab, check Manual and Counts, then enter an appropriate value.

Step 2: Generation of high-resolution PDF files using PDFCreator


To convert the work sheet into a high resolution PDF file, click on File --> Print. Select the PDFCreator as the printer and click OK. When the dialog of the PDFCreator shows up, click Options to configure how the PDF files will be generated. This has to be done only once at the first use. On the left side in the menu Formats click on PDF, then on the Compression tab. Check Compress Text Objects and check Compress for all three types of images indicated; always select ZIP as compression mode. Make sure Resample is always unchecked. Now click Save to get back to the previous dialog. Click Save to save the PDF file and select the folder where the file should be stored.

Step 3: Export of images into a desired application (e.g., presentation tool such as PowerPoint) using Acrobat Reader


Open the PDF file with Adobe Acrobat Reader to select and copy the desired plots to any other application. The PDF file created in step 2 contains vector graphics, which even at high levels of zoom will be perfectly sharp and not pixelated. Figure 1 shows a comparison between a plot created by FACSDiva’s export function and a plot generated using our Diva-Fit strategy—the difference is obvious. Additionally, PDF files are well suited to archival for later use or to be sent by email, as they can be easily viewed on any computer without the need to have FACSDiva installed.

Figure 1. Diva-Fit facilitates generation of high-quality FACS plots. Even at the relatively low magnification shown, the image generated using the export function of FACSDiva (File --> Export --> Worksheet Elements) is strongly pixelated (left). In striking contrast, the high-resolution graph generated using our Diva-Fit strategy (right) appears very sharp. The depiction of single cells as squares is definite and therefore remains unaltered.

2009-4-en-Weber_Figure1.png


To simplify the export of plots, the resolution in Acrobat Reader should be set to a fixed value. Click Edit --> Preferences and select the category General, check the option Use fixed resolution for Snapshot tool images and enter the value 720 pixel/inch. This is the highest value allowed by Acrobat Reader. Click OK.

Now use the Snapshot tool to copy a FACS plot to the clipboard (Tools --> Select&View --> SnapshotTool). Press and hold down the left mouse button to mark the desired FACS plot. Acrobat Reader then automatically copies the marked area to the clipboard.

Now open the application where the plot should be pasted to, such as PowerPoint or Word and click edit --> paste. The FACS plot will appear in high resolution, as a 720 pixel/inch bitmap.

Part 2: How to generate histogram overlays using GIMP (based upon Part 1)

If a histogram overlay needs to be created, the respective plots have to be pasted into and processed within a graphic-editing program able to create overlays, such as GIMP. First, copy histogram 1 to the clipboard using Acrobat Reader and paste it as a new image into GIMP. To do so, open GIMP and click File --> Create --> From Clipboard in the menu bar.

Now switch back to Acrobat Reader and copy histogram 2 to the clipboard (which has ideally been set to another color in FACSDiva beforehand). Make sure both histograms are of the same size (see step one); this is essential. Histogram 2 has to be pasted as a new layer into the same image file of GIMP. To do so, click Edit --> Paste as --> New Layer.

The image file now contains the two histograms lying on top of each other in two Layers. In the layers dialog of GIMP (usually at the right side, otherwise press Ctrl+L) the two layers are shown as well as the Layer Mode (set to Normal as default). The mode determines how the layers interact with each other and may be used to combine the two histograms into one overlay graph. To this aim, set the layer Mode to Multiply. Now both layers are visible at the same time, but not yet aligned. To align both histograms, set the Zoom function to 100% (View --> Zoom --> 100%). Select the Move Tool (Tools --> Transform Tools --> Move), click on one of the histograms and use the cursor keys of your keyboard to move it until both histograms are fully aligned.

Set the Zoom back to about 33% (View --> Zoom --> 33%) to see the entire histogram overlay. If the two histograms had different titles, the overlay may result in an unreadable text mixture. This can be initially avoided in FACSDiva (by applying identical or no titles), or corrected in GIMP, e.g., by using the Eraser Tool (Tools --> Paint Tools --> Eraser).

To save the image, click on File --> Save as, enter a filename such as Overlay1.tif to save the file as a TIFF image. Now select a folder and click OK. In the next dialog choose merge visible layers, and then check LZW to use a lossless compression for the TIFF-file. This saves space without reducing image quality. In the supplemental material hints are given how the design of histogram overlays could be altered.

In Figure 2, an example is provided in which a fusion protein consisting of EGFP and ZeoR has been expressed in 293T cells using LeGO vectors [4]. The histogram overlay shows transduced cells before and after selection with zeocin.

Figure 2. Straightforward composition of histogram overlays. 293T cells were transduced with a LeGO vector [4], encoding a fusion protein consisting of EGFP and ZeoR (Weber et al., submitted). Gene transfer reached 10%, i.e., 90% of the cells remained EGFP-negative (dark grey histogram). After selection with Zeocin, almost all remaining cells were EGFP-positive (99.8%; green histogram).

2009-4-en-Weber_Figure2.png


Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)


Here we describe two possibilities of fulfilling this task: the first one is a bit easier, but the second one uses free software (see Figure 3).

Figure 3. Removal of annotations within plots, absolutely residue-free. Annotations within plots may hide cells and disturb a clear figure (left plot). Unfortunately, in FACSDiva it is impossible to disable, hide, or delete quadrant labels. As illustrated, Diva-Fit can quickly remove unwanted labels, residue-free, without modifying a single dot of the dot plot (right plot).

2009-4-en-Weber_Figure3.png

Although it is not free, Adobe Acrobat is available in many labs. Removal of labels from FACS plots with this software is quite convenient. Please note that the described procedure does not work with the free Adobe Acrobat Reader. Open the PDF file generated by PDFCreator in Adobe Acrobat. Click on Tools --> Advanced Editing --> TouchUp Text Tool. Then click on the label you want to remove. Now the text of that label can be deleted or even modified as you like. The modified PDF file can be saved if desired. The export of the modified plots into other programs works as described in part 1 of this manual.

The alternative possibility relies on Inkscape, which needs to be installed on the computer. Start Inkscape and open the PDF file generated by PDFCreator (File --> Open). If the PDF contains more than one page, select which page to import at the top of the dialog box and click OK. Inkscape now shows the content of the PDF file as a single element. Fortunately, it is able to ungroup the vector elements of the plots. Right click on a plot and choose Ungroup.  After the ungrouping all single elements are selected. Now select the labels that should be deleted and press delete on the keyboard. If the element you want to delete cannot be selected separately, try to ungroup it again (right click --> Ungroup). Since Inkscape is able to individually remove the vector element containing the quadrant labels, it leaves the dots/cells completely untouched (for more details please refer to the Supplement).

The modified plot can easily be exported as a high-resolution bitmap file. Press and hold down the left mouse button to mark the entire FACS plot. Then click on File --> Export Bitmap. The export dialog automatically is set to Selection—thus the selected plot will be exported exclusively. Also, the desired resolution can be set in the export dialog – 600 dpi (up to 1200 dpi is possible) is a good value. Now click on Browse to choose a folder where the file should be stored in and click on Export. Inkscape always exports bitmaps as PNG files which can be easily used in almost every other application (like PowerPoint or Word) or converted to TIFF files without loss of quality using GIMP.

Discussion

Graphical presentation of FCM data acquired and/or processed using FACSDiva software often suffers from low quality, since plots generated with this software frequently appear pixelated, in particular at large magnifications (e.g., at poster size). This is most unfortunate, since high-quality presentation is a sine qua non for adequate perception and publication of any data [3].

We have developed an easy and straightforward toolbox, Diva-Fit, for the high-quality presentation of FCM data obtained/processed with FACSDiva. To do so, we utilize the built-in high quality print function of FACSDiva software and adapt it to create high-resolution graphs in PDF format with a much superior quality. Importantly, these high-quality illustrations can easily be included into any presentation format, e.g., MS Word, PowerPoint or similar applications. Additionally, the PDF format is very convenient for storage and exchange of data, since it can be viewed and processed on computers not equipped with FACSDiva.

Diva-Fit might be particularly interesting for many researchers in the field who require fast and convenient generation of histogram overlays, a feature badly missed in all FACSDiva versions. It needs to be noted that there are commercially available programs which might be used to re-analyze FCS files obtained with FACSDiva, e.g. in order to create overlay plots. Programs such as FlowJo (Tree Star, Ashland, OR) are powerful tools with multiple features. However, besides the significant costs for obtaining additional software, its operation is usually quite complex and requires additional training. In contrast, the toolbox described here was essentially developed in order to present data obtained with FACSDiva at better quality. A typical further example for such application is the opportunity to easily delete or modify perturbing annotations automatically set by FACSDiva, e.g. quadrant labels, using Diva-Fit.

In conclusion, we believe that Diva-Fit will be valuable for many users of BD flow cytometers equipped with FACSDiva software in optimizing FCM data presentation.

Supplementary material

Acknowledgement

This work was supported by the Deutsche Forschungsgemeinschaft (DFG-FE568/11-1). This work is part of the doctoral thesis of Kristoffer Weber.

References

1. Shapiro HM. Practical Flow Cytometry. John Wiley & Sons Inc. 2003.

2. https://lists.purdue.edu/pipermail/cytometry/2004-January/025976.html (May 15, 2009);
https://lists.purdue.edu/pipermail/cytometry/2007-November/033816.html (May 15, 2009).

3. Neill US. How to write a scientific masterpiece. J Clin Invest 2007;117:3599-3602. doi:10.1172/JCI34288Open Access

4. Weber K, Bartsch U, Stocking C, Fehse B. A multi-color panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis. Mol Ther. 2008;16:698–706. doi: 10.1038/mt.2008.6Open Access (Supplemental information)

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Supplementary material

Introduction

Flow cytometry (FCM), often referred to as Fluorescence Activated Cell Sorting (FACS) has developed into a highly sophisticated cell analysis method, which facilitates the concurrent analysis of multiple cell parameters [1]. At the same time and most surprisingly, graphical presentation of FCM data is often characterized by low-quality images.

In particular, FACSDiva software has two major drawbacks: First, even the latest version does not support generation of histogram overlays. Since histogram overlays represent a convenient way of directly comparing FCM data, this is often considered a main disadvantage of the software [2]. Secondly, FACSDiva does not allow the export of high-resolution image files of any type; neither copy/paste, nor Export Worksheet Elements result in satisfying image quality. Notably, even the new built-in Save as PDF function of FACSDiva is not able to generate high-resolution, vector-based images – instead it combines the low-resolution raster/pixel graphics in a PDF file. At the same time, FACSDiva software supports high-resolution printing of FACS plots, as can easily be seen on any printout generated with the software.

Since adequate, high-quality data presentation is an important precondition for publishing research results [3], we asked whether we could develop an easy manual for generating high-quality graphs for data obtained with FACSDiva. The basic idea of this manual is to trick FACSDiva by using its print functionality to generate a high-resolution, vector-based PDF file. Notably, conferring FACS plots into PDF files not only represents a convenient way of storing FCM data in an easy accessible format, but also allows the FACS plots to be later extracted in high-resolution quality, perfectly suitable for any kind of publication including large posters.

We here describe a Figure-improvement toolbox (Diva-Fit), which we find to be easy, fast and convenient. This toolbox facilitates the export of FACS data obtained with FACSDiva into high-resolution PDF files, the removal of unwanted quadrant labels (automatically adhered by FACSDiva) and the generation of histogram overlays. Importantly, all of the software used is distributed free of charge. It should be noted that the described strategy may also be performed by combining alternative programs to the ones used here. However, in exploring various tools we found the way described below to be the most convenient. In fact, with some experience even generation of high-resolution histogram overlays takes only a few minutes using the proposed protocol.

Material and Methods

Software tools used
Diva-Fit requires several programs to be installed on the computer. We made sure that, with the exception of FACSDiva, the required software is free of charge and can easily be obtained from Internet sources. Administrative rights are necessary to install the software. If you do not have enough rights to install software, ask your local system administrator.

The following programs have been used:

BD FACSDiva 6.1.2
Any version should work

PDFCreator 0.9.5
http://www.pdfforge.org/products/pdfcreator
This version or newer is recommended. Alternatively, other PDF printer drivers possibly already installed on the computer could be used (e.g., Adobe Acrobat comes with a PDF printer driver, the free Acrobat Reader does not). However, the method will be different.

Adobe Acrobat Reader 9.1.0
http://get.adobe.com/uk/reader/otherversions/
We recommend using this version or newer.

GIMP 2.6.4
http://www.gimp.org/downloads/
GIMP is only necessary for the creation of histogram overlays. This version or newer is recommended; however, older versions should work too. Alternatively, Adobe Photoshop could be used; the treatment is only slightly different. Not every image manipulation program offers all necessary features. GIMP is a very powerful program, but quite demanding because of its complexity.

Inkscape 0.46
http://www.inkscape.org/download/
Inkscape is only necessary for the deletion of text within plots (e.g., quadrant labels). The most recent version should be used: version 0.46 or newer. Inkscape is a vector graphics editor that is also capable of modifying the content of PDF files. The low version number (0.46) represents the ongoing development status, and not everything works perfectly yet. Nevertheless, this program has a lot of features and is quite difficult to use.

Results

Diva-Fit, a toolbox for the generation of high-resolution FCM graphs
In this result section all steps of our manual are described in a concise form. For those researchers less familiar with the software tools we used, a very detailed description including screenshots is provided in the supplementary material. Part 1 describes how to generate high-resolution dot plots and histograms. Part 2 describes how to generate histogram overlays (this is based upon Part 1). Part 3 describes how to delete text within plots, e.g., quadrant labels in dot plots (also based upon Part 1).

Part 1: How to extract high-resolution dot plots and histograms from BD’s FACSDiva

Step 1: Obtaining and processing data with FACSDiva


FCM data are obtained and processed using FACSDiva. Dependent on the required style of final data presentation, dot or histogram plots can be designed. Importantly, if a histogram overlay needs to be created, it is essential to make the histograms the same size and to set the scaling of the Y-axis to identical values. To do so, mark both histograms and click the button Make Same Size. Then go to the Inspector (View --> Inspector) and at the Histogram tab, check Manual and Counts, then enter an appropriate value.

Step 2: Generation of high-resolution PDF files using PDFCreator


To convert the work sheet into a high resolution PDF file, click on File --> Print. Select the PDFCreator as the printer and click OK. When the dialog of the PDFCreator shows up, click Options to configure how the PDF files will be generated. This has to be done only once at the first use. On the left side in the menu Formats click on PDF, then on the Compression tab. Check Compress Text Objects and check Compress for all three types of images indicated; always select ZIP as compression mode. Make sure Resample is always unchecked. Now click Save to get back to the previous dialog. Click Save to save the PDF file and select the folder where the file should be stored.

Step 3: Export of images into a desired application (e.g., presentation tool such as PowerPoint) using Acrobat Reader


Open the PDF file with Adobe Acrobat Reader to select and copy the desired plots to any other application. The PDF file created in step 2 contains vector graphics, which even at high levels of zoom will be perfectly sharp and not pixelated. Figure 1 shows a comparison between a plot created by FACSDiva’s export function and a plot generated using our Diva-Fit strategy—the difference is obvious. Additionally, PDF files are well suited to archival for later use or to be sent by email, as they can be easily viewed on any computer without the need to have FACSDiva installed.

Figure 1. Diva-Fit facilitates generation of high-quality FACS plots. Even at the relatively low magnification shown, the image generated using the export function of FACSDiva (File --> Export --> Worksheet Elements) is strongly pixelated (left). In striking contrast, the high-resolution graph generated using our Diva-Fit strategy (right) appears very sharp. The depiction of single cells as squares is definite and therefore remains unaltered.

2009-4-en-Weber_Figure1.png


To simplify the export of plots, the resolution in Acrobat Reader should be set to a fixed value. Click Edit --> Preferences and select the category General, check the option Use fixed resolution for Snapshot tool images and enter the value 720 pixel/inch. This is the highest value allowed by Acrobat Reader. Click OK.

Now use the Snapshot tool to copy a FACS plot to the clipboard (Tools --> Select&View --> SnapshotTool). Press and hold down the left mouse button to mark the desired FACS plot. Acrobat Reader then automatically copies the marked area to the clipboard.

Now open the application where the plot should be pasted to, such as PowerPoint or Word and click edit --> paste. The FACS plot will appear in high resolution, as a 720 pixel/inch bitmap.

Part 2: How to generate histogram overlays using GIMP (based upon Part 1)

If a histogram overlay needs to be created, the respective plots have to be pasted into and processed within a graphic-editing program able to create overlays, such as GIMP. First, copy histogram 1 to the clipboard using Acrobat Reader and paste it as a new image into GIMP. To do so, open GIMP and click File --> Create --> From Clipboard in the menu bar.

Now switch back to Acrobat Reader and copy histogram 2 to the clipboard (which has ideally been set to another color in FACSDiva beforehand). Make sure both histograms are of the same size (see step one); this is essential. Histogram 2 has to be pasted as a new layer into the same image file of GIMP. To do so, click Edit --> Paste as --> New Layer.

The image file now contains the two histograms lying on top of each other in two Layers. In the layers dialog of GIMP (usually at the right side, otherwise press Ctrl+L) the two layers are shown as well as the Layer Mode (set to Normal as default). The mode determines how the layers interact with each other and may be used to combine the two histograms into one overlay graph. To this aim, set the layer Mode to Multiply. Now both layers are visible at the same time, but not yet aligned. To align both histograms, set the Zoom function to 100% (View --> Zoom --> 100%). Select the Move Tool (Tools --> Transform Tools --> Move), click on one of the histograms and use the cursor keys of your keyboard to move it until both histograms are fully aligned.

Set the Zoom back to about 33% (View --> Zoom --> 33%) to see the entire histogram overlay. If the two histograms had different titles, the overlay may result in an unreadable text mixture. This can be initially avoided in FACSDiva (by applying identical or no titles), or corrected in GIMP, e.g., by using the Eraser Tool (Tools --> Paint Tools --> Eraser).

To save the image, click on File --> Save as, enter a filename such as Overlay1.tif to save the file as a TIFF image. Now select a folder and click OK. In the next dialog choose merge visible layers, and then check LZW to use a lossless compression for the TIFF-file. This saves space without reducing image quality. In the supplemental material hints are given how the design of histogram overlays could be altered.

In Figure 2, an example is provided in which a fusion protein consisting of EGFP and ZeoR has been expressed in 293T cells using LeGO vectors [4]. The histogram overlay shows transduced cells before and after selection with zeocin.

Figure 2. Straightforward composition of histogram overlays. 293T cells were transduced with a LeGO vector [4], encoding a fusion protein consisting of EGFP and ZeoR (Weber et al., submitted). Gene transfer reached 10%, i.e., 90% of the cells remained EGFP-negative (dark grey histogram). After selection with Zeocin, almost all remaining cells were EGFP-positive (99.8%; green histogram).

2009-4-en-Weber_Figure2.png


Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)


Here we describe two possibilities of fulfilling this task: the first one is a bit easier, but the second one uses free software (see Figure 3).

Figure 3. Removal of annotations within plots, absolutely residue-free. Annotations within plots may hide cells and disturb a clear figure (left plot). Unfortunately, in FACSDiva it is impossible to disable, hide, or delete quadrant labels. As illustrated, Diva-Fit can quickly remove unwanted labels, residue-free, without modifying a single dot of the dot plot (right plot).

2009-4-en-Weber_Figure3.png

Although it is not free, Adobe Acrobat is available in many labs. Removal of labels from FACS plots with this software is quite convenient. Please note that the described procedure does not work with the free Adobe Acrobat Reader. Open the PDF file generated by PDFCreator in Adobe Acrobat. Click on Tools --> Advanced Editing --> TouchUp Text Tool. Then click on the label you want to remove. Now the text of that label can be deleted or even modified as you like. The modified PDF file can be saved if desired. The export of the modified plots into other programs works as described in part 1 of this manual.

The alternative possibility relies on Inkscape, which needs to be installed on the computer. Start Inkscape and open the PDF file generated by PDFCreator (File --> Open). If the PDF contains more than one page, select which page to import at the top of the dialog box and click OK. Inkscape now shows the content of the PDF file as a single element. Fortunately, it is able to ungroup the vector elements of the plots. Right click on a plot and choose Ungroup.  After the ungrouping all single elements are selected. Now select the labels that should be deleted and press delete on the keyboard. If the element you want to delete cannot be selected separately, try to ungroup it again (right click --> Ungroup). Since Inkscape is able to individually remove the vector element containing the quadrant labels, it leaves the dots/cells completely untouched (for more details please refer to the Supplement).

The modified plot can easily be exported as a high-resolution bitmap file. Press and hold down the left mouse button to mark the entire FACS plot. Then click on File --> Export Bitmap. The export dialog automatically is set to Selection—thus the selected plot will be exported exclusively. Also, the desired resolution can be set in the export dialog – 600 dpi (up to 1200 dpi is possible) is a good value. Now click on Browse to choose a folder where the file should be stored in and click on Export. Inkscape always exports bitmaps as PNG files which can be easily used in almost every other application (like PowerPoint or Word) or converted to TIFF files without loss of quality using GIMP.

Discussion

Graphical presentation of FCM data acquired and/or processed using FACSDiva software often suffers from low quality, since plots generated with this software frequently appear pixelated, in particular at large magnifications (e.g., at poster size). This is most unfortunate, since high-quality presentation is a sine qua non for adequate perception and publication of any data [3].

We have developed an easy and straightforward toolbox, Diva-Fit, for the high-quality presentation of FCM data obtained/processed with FACSDiva. To do so, we utilize the built-in high quality print function of FACSDiva software and adapt it to create high-resolution graphs in PDF format with a much superior quality. Importantly, these high-quality illustrations can easily be included into any presentation format, e.g., MS Word, PowerPoint or similar applications. Additionally, the PDF format is very convenient for storage and exchange of data, since it can be viewed and processed on computers not equipped with FACSDiva.

Diva-Fit might be particularly interesting for many researchers in the field who require fast and convenient generation of histogram overlays, a feature badly missed in all FACSDiva versions. It needs to be noted that there are commercially available programs which might be used to re-analyze FCS files obtained with FACSDiva, e.g. in order to create overlay plots. Programs such as FlowJo (Tree Star, Ashland, OR) are powerful tools with multiple features. However, besides the significant costs for obtaining additional software, its operation is usually quite complex and requires additional training. In contrast, the toolbox described here was essentially developed in order to present data obtained with FACSDiva at better quality. A typical further example for such application is the opportunity to easily delete or modify perturbing annotations automatically set by FACSDiva, e.g. quadrant labels, using Diva-Fit.

In conclusion, we believe that Diva-Fit will be valuable for many users of BD flow cytometers equipped with FACSDiva software in optimizing FCM data presentation.

Supplementary material

Acknowledgement

This work was supported by the Deutsche Forschungsgemeinschaft (DFG-FE568/11-1). This work is part of the doctoral thesis of Kristoffer Weber.

References

1. Shapiro HM. Practical Flow Cytometry. John Wiley & Sons Inc. 2003.

2. https://lists.purdue.edu/pipermail/cytometry/2004-January/025976.html (May 15, 2009);
https://lists.purdue.edu/pipermail/cytometry/2007-November/033816.html (May 15, 2009).

3. Neill US. How to write a scientific masterpiece. J Clin Invest 2007;117:3599-3602. doi:10.1172/JCI34288Open Access

4. Weber K, Bartsch U, Stocking C, Fehse B. A multi-color panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis. Mol Ther. 2008;16:698–706. doi: 10.1038/mt.2008.6Open Access (Supplemental information)

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["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "20" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13935" ["VALUE"]=> string(22) "05/26/2009 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "05/26/2009 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "21" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13936" ["VALUE"]=> string(22) "07/03/2009 12:00:00 am" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(22) "07/03/2009 12:00:00 am" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "22" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> 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["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> array(2) { [0]=> string(5) "14106" [1]=> string(5) "14107" } ["VALUE"]=> array(2) { [0]=> string(3) "985" [1]=> string(2) "41" } ["DESCRIPTION"]=> array(2) { [0]=> string(0) "" [1]=> string(0) "" } ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { [0]=> string(3) "985" [1]=> string(2) "41" } ["~DESCRIPTION"]=> array(2) { [0]=> string(0) "" [1]=> string(0) "" } ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13940" ["VALUE"]=> array(2) { ["TEXT"]=> string(47) "<p>Вебер К., Фезе Б.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(35) "

Вебер К., Фезе Б.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13941" ["VALUE"]=> array(2) { ["TEXT"]=> string(3678) "<p class="bodytext">За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину (&quot;наложенная гистограмма&quot;) – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.        <br /><br />Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3642) "

За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину ("наложенная гистограмма") – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.       

Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии." ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13942" ["VALUE"]=> string(29) "10.3205/ctt-2009-en-000045.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2009-en-000045.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13953" ["VALUE"]=> array(2) { ["TEXT"]=> string(48) "<p>Kristoffer Weber, Boris Fehse</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(36) "

Kristoffer Weber, Boris Fehse

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13963" ["VALUE"]=> array(2) { ["TEXT"]=> string(919) "<p class="bodytext">Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany </p> <br/> <p class="bodytext"><b>Correspondence:</b><br> Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany<br> Phone: +49-40-7410-52705 / +49-40-7410-55518<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.o2aifivDyoi2hi');">k.weber@<span style="display:none;">spam is bad</span>uke.de</a> or <a href="javascript:linkTo_UnCryptMailto('qempxs.jilwiDyoi2hi');">fehse@<span style="display:none;">spam is bad</span>uke.de</a> <sup><br /></sup> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(733) "

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

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In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.

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["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13953" ["VALUE"]=> array(2) { ["TEXT"]=> string(48) "<p>Kristoffer Weber, Boris Fehse</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(36) "

Kristoffer Weber, Boris Fehse

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Kristoffer Weber, Boris Fehse

" } ["SUMMARY_EN"]=> array(37) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14004" ["VALUE"]=> array(2) { ["TEXT"]=> string(1362) "<p class="bodytext">In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1340) "

In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(1340) "

In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13942" ["VALUE"]=> string(29) "10.3205/ctt-2009-en-000045.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2009-en-000045.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(29) "10.3205/ctt-2009-en-000045.01" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13943" ["VALUE"]=> string(147) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(147) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(147) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "13963" ["VALUE"]=> array(2) { ["TEXT"]=> string(919) "<p class="bodytext">Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany </p> <br/> <p class="bodytext"><b>Correspondence:</b><br> Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany<br> Phone: +49-40-7410-52705 / +49-40-7410-55518<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.o2aifivDyoi2hi');">k.weber@<span style="display:none;">spam is bad</span>uke.de</a> or <a href="javascript:linkTo_UnCryptMailto('qempxs.jilwiDyoi2hi');">fehse@<span style="display:none;">spam is bad</span>uke.de</a> <sup><br /></sup> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(733) "

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

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Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

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Вебер К., Фезе Б.

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Вебер К., Фезе Б.

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["VALUE"]=> array(2) { ["TEXT"]=> string(3678) "<p class="bodytext">За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину (&quot;наложенная гистограмма&quot;) – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.        <br /><br />Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3642) "

За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину ("наложенная гистограмма") – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.       

Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии." ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(3642) "

За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину ("наложенная гистограмма") – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.       

Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии." } } } [7]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "45" ["~IBLOCK_SECTION_ID"]=> string(2) "45" ["ID"]=> string(3) "993" ["~ID"]=> string(3) "993" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(339) "Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение." ["~NAME"]=> string(339) "Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение." ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "07/25/2017 03:21:35 pm" ["~TIMESTAMP_X"]=> string(22) "07/25/2017 03:21:35 pm" ["DETAIL_PAGE_URL"]=> string(123) "/en/archive/tom-1-nomer-4/metody/diva-fit-poetapnoe-rukovodstvo-k-postroeniyu-grafikov-i-gistogramm-s-vysokim-razresheniem/" ["~DETAIL_PAGE_URL"]=> string(123) "/en/archive/tom-1-nomer-4/metody/diva-fit-poetapnoe-rukovodstvo-k-postroeniyu-grafikov-i-gistogramm-s-vysokim-razresheniem/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(21944) "

Part 1: A detailed description of Diva-Fit - how to extract high resolution dot plots and histograms from BD’s FACSDiva software

The FACSDiva software itself is unable to export any high-resolution image files; neither copy/paste, nor Export Worksheet Elements result in satisfying image quality. Interestingly, even the new built-in Save as PDF function of FACSDiva is not able to generate such high resolution, vector-based files – instead it combines the low-resolution raster/pixel graphics in a PDF file. However, FACSDiva supports high-resolution printing, as can easily be seen on any printout generated with the software. In this supplement a detailed description shows how FACSDiva can be “tricked” into producing high-resolution images, using its print functionality and a vector-based PDF file as intermediate step. Below we describe the Diva-Fit procedure step-by-step. With some experience, even the generation of high-resolution histogram overlays will only take a few minutes using Diva-Fit.

Our proposed strategy (Diva-Fit) requires several programs to be installed on the computer. We made sure that, with the exception of FACSDiva, the required software is free of charge and can be easily obtained via download. Administrative rights are necessary to install the software. If you do not have enough rights to install software, ask your local system administrator to install the following software tools.

BD FACSDiva 6.1.2 (any version should work)

PDFCreator 0.9.5
http://www.pdfforge.org/products/pdfcreator
This version or newer is recommended. Alternatively, other PDF printer drivers possibly already installed on the computer could be used (e.g., Adobe Acrobat comes with a PDF printer driver; the free Acrobat Reader does not). However, the method will be different.

Adobe Acrobat Reader 9.1.0
http://get.adobe.com/uk/reader/otherversions/
We recommend this version or newer. Older versions may not provide all the features required.

Step 1: Obtaining and processing data with FACSDiva
Prepare your FACS analysis in FACSDiva as usual. This example shows cells expressing a fusion protein consisting of EGFP and ZeoR, rendering the cells EGFP positive and resistant to zeocin (lower panels after selection). Importantly, if a histogram overlay needs to be created, it is essential to make the histograms the same size and to set the scaling of the Y-axis to identical values. To do so, mark both histograms and click the button Make Same Size. Then go to the Inspector (View --> Inspector) and at the Histogram tab, check Manual and Counts, then enter an appropriate value.

2009-4-en-Weber-et-al-Suppl-Image01.png

2009-4-en-Weber-et-al-Suppl-Image02.png
2009-4-en-Weber-et-al-Suppl-Image03.png

Step 2: Generation of high-resolution PDF files using PDFCreator
To convert the work sheet into a high resolution PDF file, click on File --> Print. Select PDFCreator as the printer and click OK.

2009-4-en-Weber-et-al-Suppl-Image04.png

2009-4-en-Weber-et-al-Suppl-Image05.png

When the dialog of PDFCreator shows up, click Options to configure how the PDF files will be generated. This only has to be done the first time.

2009-4-en-Weber-et-al-Suppl-Image06.png

In the Formats menu, click on PDF, then on the Compression tab. Adjust the compression settings according to the picture below (check Compress Text Objects and check Compress for all three types of images, always select ZIP as compression mode). Make sure Resample is always unchecked. Now click Save to get back to the previous dialog.

2009-4-en-Weber-et-al-Suppl-Image07.png

Click Save to save the PDF file and select the folder where the file should be stored.

2009-4-en-Weber-et-al-Suppl-Image08.png

2009-4-en-Weber-et-al-Suppl-Image09_01.png

Step 3: Export of images into a desired application (e.g., presentation tool such as PowerPoint) using Acrobat Reader
Open the PDF file in Adobe Acrobat Reader to select and copy the desired plots to any other application. This PDF file contains vector graphics and even at high levels of zoom the text will be perfectly sharp and not pixelated.

2009-4-en-Weber-et-al-Suppl-Image10.png

The next two pictures show a comparison between the PDF file created by PDFCreator and a PDF file created by FACSDiva using its Save as PDF function – the difference is obvious. Additionally, these PDF files are well suited to archival for later use or to be sent by email as they can be easily viewed without the need to have FACSDiva installed.

2009-4-en-Weber-et-al-Suppl-Image11_small.PNG

2009-4-en-Weber-et-al-Suppl-Image12_small.png

Below you see the PDF file containing vector graphics zoomed to 1200%. It stays perfectly sharp; no pixelation is visible. In contrast to FACSDiva, Acrobat Reader allows the export of FACS plots in high resolution raster graphics suitable for use in presentations or as publication-quality figures in other graphics editing programs or office suites, and/or for high quality prints.

2009-4-en-Weber-et-al-Suppl-Image13_small.png

To simplify the export of plots in Acrobat Reader, the resolution should be set to a fixed value. Click Edit --> Preferences and select the category General, check the option Use fixed resolution for Snapshot tool images and enter the value 720 pixel/inch. This is the highest value allowed by Acrobat Reader. Click OK.

2009-4-en-Weber-et-al-Suppl-Image14.png

2009-4-en-Weber-et-al-Suppl-Image15.png

Now use the Snapshot tool to copy a FACS plot to the clipboard (Tools --> Select&View --> SnapshotTool). Press and hold down the left mouse button to mark the desired FACS plot. Acrobat Reader will automatically copy the marked area to the clipboard (720 pixel/inch).

2009-4-en-Weber-et-al-Suppl-Image16.png

Now open the application where the plot should be used, such as PowerPoint or Word, and click edit --> paste. The FACS plot will appear in high resolution, as a 720 pixel/inch bitmap.

Part 2: How to generate histogram overlays (based upon Part 1)
Additional software is needed for part 2, which is also available free:

GIMP 2.6.4
http://www.gimp.org/downloads/
GIMP is only required for the creation of histogram overlays. This version or newer is recommended; however, older versions should work, too. Alternatively, Adobe Photoshop could be used; the treatment is only slightly different. However, not every image manipulation program offers all necessary features. GIMP is very powerful software, but quite demanding because of its complexity.

If a histogram overlay should be created, the plot has to be pasted into a graphic-editing program able to create overlays, as GIMP can. Use Acrobat reader to copy the first histogram to the clipboard (as described in part 1) and paste it as a new image in GIMP. To do so, open GIMP and click File --> Create --> From Clipboard.

2009-4-en-Weber-et-al-Suppl-Image17.png

Next, copy the second histogram to the clipboard (which has ideally been set to another color in FACSDiva beforehand). Make sure both histograms are of the same size; this is essential (see step one).

2009-4-en-Weber-et-al-Suppl-Image18.png

This second histogram has to be pasted as a new layer into the same image file of GIMP, to do so click Edit --> Paste as --> New Layer.

2009-4-en-Weber-et-al-Suppl-Image19.png

The image file now contains the two histograms collocated on top of each other in two Layers. In the layers dialog (see red circle) the two layers are shown as well as their current Mode (set to Normal as default). The mode determines how the layers interact with each other and can thus be used to combine the two histograms into an overlay graph.

2009-4-en-Weber-et-al-Suppl-Image20.png

As a first step, set Mode to Multiply. Now both layers are visible, but not yet aligned.

2009-4-en-Weber-et-al-Suppl-Image21.png

To align both histograms, set the Zoom to 100% (see lower red circle). Select the Move Tool (see upper red circle), click somewhere on the histogram to activate the given window and use the cursor keys of your keyboard to move one histogram until both histograms are aligned.

2009-4-en-Weber-et-al-Suppl-Image22.png

2009-4-en-Weber-et-al-Suppl-Image23.png

Set the Zoom back to about 33% to see the entire histogram overlay. If the titles of the two histograms were different, a mixed and therefore unreadable overlay of text will appear. This can be avoided in FACSDiva from the start (identical or no titles) or corrected in GIMP, e.g., by using the Eraser Tool.

2009-4-en-Weber-et-al-Suppl-Image24.png

To save the image, click on File --> Save as, enter a filename such as Overlay1.tif to save the file as a TIFF image. Now select a folder and click OK. In the next dialog choose merge visible layers, and then check LZW to use a lossless compression for the TIFF-file. This saves space without reducing image quality.

Part 2 B (optional): Further modifications
If desired, the appearance of the overlay can be altered in many ways. Setting the Mode for example to Darken only changes the way the two layers are combined (compare detail in red circle).

2009-4-en-Weber-et-al-Suppl-Image25.png

For another modification, in the layers dialog click on the layer with the grey histogram…

2009-4-en-Weber-et-al-Suppl-Image26.png

…and then choose Colors --> Levels.

2009-4-en-Weber-et-al-Suppl-Image27.png

In the Levels dialog, the grey histogram could be turned into black by moving the black triangle to the right (see red circle).

2009-4-en-Weber-et-al-Suppl-Image28.png

Alternatively, it could be made transparent by moving the white triangle to the left (see red circle).

2009-4-en-Weber-et-al-Suppl-Image29.png

Part 3: How to delete quadrant labels (Q1–Q4) in dot plots (based upon Part 1)
Additional software is needed for part 3. Only the second alternative uses free software:

Adobe Acrobat
Although it is not free, Adobe Acrobat is available in many labs and quite convenient for removing labels from FACS plots. This procedure does not work with the free Acrobat Reader. Open the PDF file generated by PDFCreator in Adobe Acrobat.
Click on Tools --> Advanced Editing --> TouchUp Text Tool. Then click on the label you want to remove. Now the text of that label can be deleted or even modified as you like. The modified PDF file can be saved if desired. The export of the modified plots into other programs works as described in part 1 of this manual.

Inkscape 0.46
http://www.inkscape.org/download/
The most recent version should be used: at least version 0.46. Inkscape is a vector graphics editor, also able to modify PDF files. The low version number (0.46) represents the ongoing development status, and not everything works perfectly yet. Nevertheless, this program has a lot of features and is quite difficult to use.

Start Inkscape and open the PDF file generated by PDFCreator (File --> Open). If the PDF contains more than one page, select which page to import (see red circle) and click OK.

2009-4-en-Weber-et-al-Suppl-Image30.png

Inkscape shows the content of the PDF file as a single element. Fortunately, it is able to ungroup the vector elements of the plots. Right click on a plot and choose Ungroup.

2009-4-en-Weber-et-al-Suppl-Image31.png

After the ungrouping all single elements are selected. The first time it might be confusing that there will also be a white square behind all the elements. This should be deleted for convenience. To do so, click somewhere outside of the marked area to unselect everything. Then click on the white background and press Del on your keyboard to delete it.

2009-4-en-Weber-et-al-Suppl-Image32.png

Now select the labels that should be deleted and press Del. In this example the quadrant names are selected. If the element you want to delete cannot be selected separately, try to ungroup it again (right click --> Ungroup).

2009-4-en-Weber-et-al-Suppl-Image33.png

Since Inkscape is able to selectively remove the vector element containing the quadrant labels, it leaves the dots/cells completely untouched.

2009-4-en-Weber-et-al-Suppl-Image34.png

The modified plot can easily be exported as a high-resolution bitmap file. Press and hold down the left mouse button to mark the entire FACS plot. Then click on File --> Export Bitmap.

2009-4-en-Weber-et-al-Suppl-Image35.png

The export dialog automatically is set to Selection – thus the selected plot will be exported exclusively. Also, the desired resolution can be set in the export dialog – 600 dpi (up to 1200 dpi is possible) is a good value (see upper red circle). Now click on Browse to choose a folder where the file should be stored, and click on Export. Inkscape always exports bitmaps as PNG files, which can be easily used in almost any other application (like PowerPoint or Word) or converted to TIFF files without a loss of quality using GIMP.

2009-4-en-Weber-et-al-Suppl-Image36.png

The exported PNG files have a high resolution; the quadrant labels are removed residue-free while the dot plot remains unaltered.

2009-4-en-Weber-et-al-Suppl-Image37.png

References

Weber K, Bartsch U, Stocking C, Fehse B. A multi-color panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis. Mol Ther 2008;16, 698–706. [http://www.LentiGO-Vectors.de]

" ["~DETAIL_TEXT"]=> string(21944) "

Part 1: A detailed description of Diva-Fit - how to extract high resolution dot plots and histograms from BD’s FACSDiva software

The FACSDiva software itself is unable to export any high-resolution image files; neither copy/paste, nor Export Worksheet Elements result in satisfying image quality. Interestingly, even the new built-in Save as PDF function of FACSDiva is not able to generate such high resolution, vector-based files – instead it combines the low-resolution raster/pixel graphics in a PDF file. However, FACSDiva supports high-resolution printing, as can easily be seen on any printout generated with the software. In this supplement a detailed description shows how FACSDiva can be “tricked” into producing high-resolution images, using its print functionality and a vector-based PDF file as intermediate step. Below we describe the Diva-Fit procedure step-by-step. With some experience, even the generation of high-resolution histogram overlays will only take a few minutes using Diva-Fit.

Our proposed strategy (Diva-Fit) requires several programs to be installed on the computer. We made sure that, with the exception of FACSDiva, the required software is free of charge and can be easily obtained via download. Administrative rights are necessary to install the software. If you do not have enough rights to install software, ask your local system administrator to install the following software tools.

BD FACSDiva 6.1.2 (any version should work)

PDFCreator 0.9.5
http://www.pdfforge.org/products/pdfcreator
This version or newer is recommended. Alternatively, other PDF printer drivers possibly already installed on the computer could be used (e.g., Adobe Acrobat comes with a PDF printer driver; the free Acrobat Reader does not). However, the method will be different.

Adobe Acrobat Reader 9.1.0
http://get.adobe.com/uk/reader/otherversions/
We recommend this version or newer. Older versions may not provide all the features required.

Step 1: Obtaining and processing data with FACSDiva
Prepare your FACS analysis in FACSDiva as usual. This example shows cells expressing a fusion protein consisting of EGFP and ZeoR, rendering the cells EGFP positive and resistant to zeocin (lower panels after selection). Importantly, if a histogram overlay needs to be created, it is essential to make the histograms the same size and to set the scaling of the Y-axis to identical values. To do so, mark both histograms and click the button Make Same Size. Then go to the Inspector (View --> Inspector) and at the Histogram tab, check Manual and Counts, then enter an appropriate value.

2009-4-en-Weber-et-al-Suppl-Image01.png

2009-4-en-Weber-et-al-Suppl-Image02.png
2009-4-en-Weber-et-al-Suppl-Image03.png

Step 2: Generation of high-resolution PDF files using PDFCreator
To convert the work sheet into a high resolution PDF file, click on File --> Print. Select PDFCreator as the printer and click OK.

2009-4-en-Weber-et-al-Suppl-Image04.png

2009-4-en-Weber-et-al-Suppl-Image05.png

When the dialog of PDFCreator shows up, click Options to configure how the PDF files will be generated. This only has to be done the first time.

2009-4-en-Weber-et-al-Suppl-Image06.png

In the Formats menu, click on PDF, then on the Compression tab. Adjust the compression settings according to the picture below (check Compress Text Objects and check Compress for all three types of images, always select ZIP as compression mode). Make sure Resample is always unchecked. Now click Save to get back to the previous dialog.

2009-4-en-Weber-et-al-Suppl-Image07.png

Click Save to save the PDF file and select the folder where the file should be stored.

2009-4-en-Weber-et-al-Suppl-Image08.png

2009-4-en-Weber-et-al-Suppl-Image09_01.png

Step 3: Export of images into a desired application (e.g., presentation tool such as PowerPoint) using Acrobat Reader
Open the PDF file in Adobe Acrobat Reader to select and copy the desired plots to any other application. This PDF file contains vector graphics and even at high levels of zoom the text will be perfectly sharp and not pixelated.

2009-4-en-Weber-et-al-Suppl-Image10.png

The next two pictures show a comparison between the PDF file created by PDFCreator and a PDF file created by FACSDiva using its Save as PDF function – the difference is obvious. Additionally, these PDF files are well suited to archival for later use or to be sent by email as they can be easily viewed without the need to have FACSDiva installed.

2009-4-en-Weber-et-al-Suppl-Image11_small.PNG

2009-4-en-Weber-et-al-Suppl-Image12_small.png

Below you see the PDF file containing vector graphics zoomed to 1200%. It stays perfectly sharp; no pixelation is visible. In contrast to FACSDiva, Acrobat Reader allows the export of FACS plots in high resolution raster graphics suitable for use in presentations or as publication-quality figures in other graphics editing programs or office suites, and/or for high quality prints.

2009-4-en-Weber-et-al-Suppl-Image13_small.png

To simplify the export of plots in Acrobat Reader, the resolution should be set to a fixed value. Click Edit --> Preferences and select the category General, check the option Use fixed resolution for Snapshot tool images and enter the value 720 pixel/inch. This is the highest value allowed by Acrobat Reader. Click OK.

2009-4-en-Weber-et-al-Suppl-Image14.png

2009-4-en-Weber-et-al-Suppl-Image15.png

Now use the Snapshot tool to copy a FACS plot to the clipboard (Tools --> Select&View --> SnapshotTool). Press and hold down the left mouse button to mark the desired FACS plot. Acrobat Reader will automatically copy the marked area to the clipboard (720 pixel/inch).

2009-4-en-Weber-et-al-Suppl-Image16.png

Now open the application where the plot should be used, such as PowerPoint or Word, and click edit --> paste. The FACS plot will appear in high resolution, as a 720 pixel/inch bitmap.

Part 2: How to generate histogram overlays (based upon Part 1)
Additional software is needed for part 2, which is also available free:

GIMP 2.6.4
http://www.gimp.org/downloads/
GIMP is only required for the creation of histogram overlays. This version or newer is recommended; however, older versions should work, too. Alternatively, Adobe Photoshop could be used; the treatment is only slightly different. However, not every image manipulation program offers all necessary features. GIMP is very powerful software, but quite demanding because of its complexity.

If a histogram overlay should be created, the plot has to be pasted into a graphic-editing program able to create overlays, as GIMP can. Use Acrobat reader to copy the first histogram to the clipboard (as described in part 1) and paste it as a new image in GIMP. To do so, open GIMP and click File --> Create --> From Clipboard.

2009-4-en-Weber-et-al-Suppl-Image17.png

Next, copy the second histogram to the clipboard (which has ideally been set to another color in FACSDiva beforehand). Make sure both histograms are of the same size; this is essential (see step one).

2009-4-en-Weber-et-al-Suppl-Image18.png

This second histogram has to be pasted as a new layer into the same image file of GIMP, to do so click Edit --> Paste as --> New Layer.

2009-4-en-Weber-et-al-Suppl-Image19.png

The image file now contains the two histograms collocated on top of each other in two Layers. In the layers dialog (see red circle) the two layers are shown as well as their current Mode (set to Normal as default). The mode determines how the layers interact with each other and can thus be used to combine the two histograms into an overlay graph.

2009-4-en-Weber-et-al-Suppl-Image20.png

As a first step, set Mode to Multiply. Now both layers are visible, but not yet aligned.

2009-4-en-Weber-et-al-Suppl-Image21.png

To align both histograms, set the Zoom to 100% (see lower red circle). Select the Move Tool (see upper red circle), click somewhere on the histogram to activate the given window and use the cursor keys of your keyboard to move one histogram until both histograms are aligned.

2009-4-en-Weber-et-al-Suppl-Image22.png

2009-4-en-Weber-et-al-Suppl-Image23.png

Set the Zoom back to about 33% to see the entire histogram overlay. If the titles of the two histograms were different, a mixed and therefore unreadable overlay of text will appear. This can be avoided in FACSDiva from the start (identical or no titles) or corrected in GIMP, e.g., by using the Eraser Tool.

2009-4-en-Weber-et-al-Suppl-Image24.png

To save the image, click on File --> Save as, enter a filename such as Overlay1.tif to save the file as a TIFF image. Now select a folder and click OK. In the next dialog choose merge visible layers, and then check LZW to use a lossless compression for the TIFF-file. This saves space without reducing image quality.

Part 2 B (optional): Further modifications
If desired, the appearance of the overlay can be altered in many ways. Setting the Mode for example to Darken only changes the way the two layers are combined (compare detail in red circle).

2009-4-en-Weber-et-al-Suppl-Image25.png

For another modification, in the layers dialog click on the layer with the grey histogram…

2009-4-en-Weber-et-al-Suppl-Image26.png

…and then choose Colors --> Levels.

2009-4-en-Weber-et-al-Suppl-Image27.png

In the Levels dialog, the grey histogram could be turned into black by moving the black triangle to the right (see red circle).

2009-4-en-Weber-et-al-Suppl-Image28.png

Alternatively, it could be made transparent by moving the white triangle to the left (see red circle).

2009-4-en-Weber-et-al-Suppl-Image29.png

Part 3: How to delete quadrant labels (Q1–Q4) in dot plots (based upon Part 1)
Additional software is needed for part 3. Only the second alternative uses free software:

Adobe Acrobat
Although it is not free, Adobe Acrobat is available in many labs and quite convenient for removing labels from FACS plots. This procedure does not work with the free Acrobat Reader. Open the PDF file generated by PDFCreator in Adobe Acrobat.
Click on Tools --> Advanced Editing --> TouchUp Text Tool. Then click on the label you want to remove. Now the text of that label can be deleted or even modified as you like. The modified PDF file can be saved if desired. The export of the modified plots into other programs works as described in part 1 of this manual.

Inkscape 0.46
http://www.inkscape.org/download/
The most recent version should be used: at least version 0.46. Inkscape is a vector graphics editor, also able to modify PDF files. The low version number (0.46) represents the ongoing development status, and not everything works perfectly yet. Nevertheless, this program has a lot of features and is quite difficult to use.

Start Inkscape and open the PDF file generated by PDFCreator (File --> Open). If the PDF contains more than one page, select which page to import (see red circle) and click OK.

2009-4-en-Weber-et-al-Suppl-Image30.png

Inkscape shows the content of the PDF file as a single element. Fortunately, it is able to ungroup the vector elements of the plots. Right click on a plot and choose Ungroup.

2009-4-en-Weber-et-al-Suppl-Image31.png

After the ungrouping all single elements are selected. The first time it might be confusing that there will also be a white square behind all the elements. This should be deleted for convenience. To do so, click somewhere outside of the marked area to unselect everything. Then click on the white background and press Del on your keyboard to delete it.

2009-4-en-Weber-et-al-Suppl-Image32.png

Now select the labels that should be deleted and press Del. In this example the quadrant names are selected. If the element you want to delete cannot be selected separately, try to ungroup it again (right click --> Ungroup).

2009-4-en-Weber-et-al-Suppl-Image33.png

Since Inkscape is able to selectively remove the vector element containing the quadrant labels, it leaves the dots/cells completely untouched.

2009-4-en-Weber-et-al-Suppl-Image34.png

The modified plot can easily be exported as a high-resolution bitmap file. Press and hold down the left mouse button to mark the entire FACS plot. Then click on File --> Export Bitmap.

2009-4-en-Weber-et-al-Suppl-Image35.png

The export dialog automatically is set to Selection – thus the selected plot will be exported exclusively. Also, the desired resolution can be set in the export dialog – 600 dpi (up to 1200 dpi is possible) is a good value (see upper red circle). Now click on Browse to choose a folder where the file should be stored, and click on Export. Inkscape always exports bitmaps as PNG files, which can be easily used in almost any other application (like PowerPoint or Word) or converted to TIFF files without a loss of quality using GIMP.

2009-4-en-Weber-et-al-Suppl-Image36.png

The exported PNG files have a high resolution; the quadrant labels are removed residue-free while the dot plot remains unaltered.

2009-4-en-Weber-et-al-Suppl-Image37.png

References

Weber K, Bartsch U, Stocking C, Fehse B. A multi-color panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis. Mol Ther 2008;16, 698–706. [http://www.LentiGO-Vectors.de]

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Вебер К., Фезе Б.

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Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение.

На английском языке

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Kristoffer Weber, Boris Fehse

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14069" ["VALUE"]=> array(2) { ["TEXT"]=> string(919) "<p class="bodytext">Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany </p> <br/> <p class="bodytext"><b>Correspondence:</b><br> Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany<br> Phone: +49-40-7410-52705 / +49-40-7410-55518<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.o2aifivDyoi2hi');">k.weber@<span style="display:none;">spam is bad</span>uke.de</a> or <a href="javascript:linkTo_UnCryptMailto('qempxs.jilwiDyoi2hi');">fehse@<span style="display:none;">spam is bad</span>uke.de</a> <sup><br /></sup> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(733) "

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14075" ["VALUE"]=> array(2) { ["TEXT"]=> string(760) "<p class="bodytext"> <strong>Here we describe all procedures depicted <a target="_blank" href="http://www.cttjournal.com/en/archive/tom-1-nomer-4/metody/diva-fit-poetapnoe-rukovodstvo-k-postroeniyu-grafikov-i-gistogramm-s-vysokim-razresheniem-dlya-anali/"><u>in the named article</u></a> in more detail.<br> </strong><br> <strong>Part 1:</strong> How to extract high-resolution dot plots and histograms from FACSDiva<br> <strong>Part 2:</strong> How to generate histogram overlays (based upon Part 1)<br> <strong>Part 3:</strong> How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1) </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(622) "

Here we describe all procedures depicted in the named article in more detail.

Part 1: How to extract high-resolution dot plots and histograms from FACSDiva
Part 2: How to generate histogram overlays (based upon Part 1)
Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14035" ["VALUE"]=> string(174) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(174) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14070" ["VALUE"]=> string(3) "674" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(3) "674" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "45" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(80) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(11) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14068" ["VALUE"]=> array(2) { ["TEXT"]=> string(48) "<p>Kristoffer Weber, Boris Fehse</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(36) "

Kristoffer Weber, Boris Fehse

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(36) "

Kristoffer Weber, Boris Fehse

" } ["SUMMARY_EN"]=> array(37) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14075" ["VALUE"]=> array(2) { ["TEXT"]=> string(760) "<p class="bodytext"> <strong>Here we describe all procedures depicted <a target="_blank" href="http://www.cttjournal.com/en/archive/tom-1-nomer-4/metody/diva-fit-poetapnoe-rukovodstvo-k-postroeniyu-grafikov-i-gistogramm-s-vysokim-razresheniem-dlya-anali/"><u>in the named article</u></a> in more detail.<br> </strong><br> <strong>Part 1:</strong> How to extract high-resolution dot plots and histograms from FACSDiva<br> <strong>Part 2:</strong> How to generate histogram overlays (based upon Part 1)<br> <strong>Part 3:</strong> How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1) </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(622) "

Here we describe all procedures depicted in the named article in more detail.

Part 1: How to extract high-resolution dot plots and histograms from FACSDiva
Part 2: How to generate histogram overlays (based upon Part 1)
Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(622) "

Here we describe all procedures depicted in the named article in more detail.

Part 1: How to extract high-resolution dot plots and histograms from FACSDiva
Part 2: How to generate histogram overlays (based upon Part 1)
Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14034" ["VALUE"]=> string(29) "10.3205/ctt-2009-en-000046.01" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(29) "10.3205/ctt-2009-en-000046.01" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(29) "10.3205/ctt-2009-en-000046.01" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14035" ["VALUE"]=> string(174) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(174) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(174) "Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14069" ["VALUE"]=> array(2) { ["TEXT"]=> string(919) "<p class="bodytext">Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany </p> <br/> <p class="bodytext"><b>Correspondence:</b><br> Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany<br> Phone: +49-40-7410-52705 / +49-40-7410-55518<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.o2aifivDyoi2hi');">k.weber@<span style="display:none;">spam is bad</span>uke.de</a> or <a href="javascript:linkTo_UnCryptMailto('qempxs.jilwiDyoi2hi');">fehse@<span style="display:none;">spam is bad</span>uke.de</a> <sup><br /></sup> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(733) "

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(733) "

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

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цитометрии, полученных посредством пакета программ FACSDiva. 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Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение.

На английском языке

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Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение.

На английском языке

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Introduction

The Philadelphia (Ph1)-chromosome was discovered in 1960 year [1] and for a long time it was considered to be a specific marker of chronic myeloid leukemia (CML). Later it was found that Ph1 is the result of reciprocal translocation between chromosomes, i.e. t(9;22)(q34;q11) [2]. In fact, this translocation results in the formation of two hybrid genes, BCR-ABL on the Ph1 chromosome and ABL-BCR on 9q+. The chimeric BCR-ABL fusion product is a tyrosine kinase. Its activity accounts for more than 95% of CML cases [3-5], and 10–20% of adults and about 2–5% of children with B-cell acute lymphoblastic leukemia (ALL) [6, 7]. Occasional bona fide Ph1-positive (Ph+) cases among acute myeloid leukemias (AML) [8, 9], lymphomas [10], multiple myeloma [11], myelodysplastic syndromes [12, 13], ‘essential thrombocythemia’ [14-16], and chronic neutrophilic leukemia (CNL) [17] have also been published.

The treatment of CML has been recently revolutionized by the development of imatinib mesylate (IMT, Gleevec, STI571) and other tyrosine kinase inhibitors (TKIs), which report to be targeted inhibitors of BCR-ABL [18-20].

I. Laboratory Tests

1.1. t(9;22)(q34;q11) translocation detection
Translocation (9;22) in newly diagnosed leukemia patients is detected using conventional cytogenetics (CC) supplemented by chromosome banding analysis (Fig. 1), and supported by reverse transcriptase polymerase chain reaction (RT-PCR) [21]. The chromosome banding analysis remains the best first-line genetic test for assessing any new acute leukemia because it screens for t(9;22) as well as for alternate and nonrandom additional genetic defects, including +der(22)t(9;22), 9p abnormalities, i(17q), -7, +8, +19, +21, and so on [21].

2009-4-en-Mamaev-Figure-1.JPG

Figure 1. Karyotype of bone marrow cell from a female patient with Ph-positive acute lymphoblastic leukemia, relapsed after allogeneic stem cell transplantation, made in Germany. It illustrates two Ph-chromosomes with typical translocation t(9;22)(q34;q11) and multiple additional numeral and structural chromosome changes. 2n=52, XX, +X, t(9;22)(q34;q11), +der(22)t(9;22), +del(4)(q27), -8, +i(8)(q10), +10, +14, -20, +der(20q+), +21.

1.2. Fluorescence in situ hybridization
One of the sensitive approaches for diagnosis of Ph+ leukemias is fluorescence in situ hybridization (FISH). The FISH technique can be applied directly to non-dividing cells, it detects both cryptic and complex BCR-ABL rearrangements, including three-way translocations as well as some breaks outside of the usual major and minor cluster regions (Fig. 2). Sensitivity of the method is about 1 cell in 200 tested, or 0.5%. A problem with around 1% of CML patients who have a Ph1-negative karyotype because of a cryptic BCR/ABL1 fusion is that it can only be located by FISH at chromosome 22q11, 9q34 or a third chromosome [22-24].

2009-4-en-Mamaev-Figure-2.JPG

Figure 2. Karyotype (A) and fluorescent in situ hybridization (FISH) analysis findings on chromosomes (B, D) and interphase nuclei (C) from a patient with chronic myeloid leukemia, illustrating atypical translocation of t(6;22)(q21;q11), which was associated with formation of fusion ABL/BCR gene on chromosome der(22)t(6;22). 2n=46, XY, t(6;22)(q21;q11). The fusion gene (yellow color) (B, C) was evidenced by means of fluorescent probes to ABL (red) and BCR (green) genes. On the other hand, the atypical translocation t(6;22) was evidenced  (D) by means of fluorescent probe WCW22 directed to chromosome number 22. After FISH each chromosome plate contains three brightly stained signals, including those on der(22)t(6;22) (small signal), unchanged chromosome 22 (right big signal) and der(6)t(6;22) (left big signal). Magnification x900.

1.3. Southern blot analysis
Southern blot analysis reliably identifies BCR gene rearrangement using probes targeting either the M-bcr or m-bcr breakpoint. Although this technique is quite helpful in confirming the BCR defect associated with CML or ALL, the Southern blot method is time-consuming and costly [22].

1.4. Amplification technologies
RT-PCR is the most sensitive of today's methods for detecting BCR-ABL. One of the advantages of RT-PCR is an ability to differentiate p210 from p190 forms of BCR-ABL [22]. It should be mentioned here that the recently developed real-time quantitative PCR (RQ-PCR) technique allows the assessment of trends in the BCR-ABL load over time and, hence, the chance to control minimal residual disease (MRD) [25]. 

1.5. Analysis of BCR-ABL kinase domain (KD) mutations
There are several molecular techniques that can detect BCR-ABL kinase domain (KD) mutations in Ph+ leukemias that are resistant to tyrosine kinase inhibitors (TKI). A more effective technique among them is a recently modified liquid chromatography (D-HPLC) [26-33].  

1.6. Gene expression profiles and micro array analysis
A major advantage of array technology is the ability to evaluate an expression of thousands of genes simultaneously. For this purpose RNA is extracted from the patient’s sample and converted to labeled cRNA or cDNA before being applied to an array of complementary probes that allows the successful differentiation of BCR-ABL cases from other forms of ALL [34].

II. Laboratory and clinical findings in Ph-positive disorders

2.1. Structure of the BCR-ABL fusion genes and their transcripts
The breakpoint in the ABL gene occurs within a >300-kb segment at the 5’end of the gene, either upstream of the first alternative exon Ib, between exons Ib and Ia, or downstream of axon Ia. In the vast majority of CML patients and in about one third of ALLs, the breakpoint in the BCR gene is revealed within a 5.8-kb region known as the major breakpoint cluster region (M-bcr), spanning 5 exons historically named b1 to b5, now known to be exons e12 to e16 of the BCR gene. Regardless of the position of the ABL breakpoint, processing of the primary BCR-ABL transcript usually results in hybrid BCR-ABL mRNA molecules with e14a2 and or e13a2 junction encoding a p210BCR-ABL fusion protein [7]. In two thirds of ALLs and in very rare cases of CML and AML patients, the breakpoint in BCR falls further upstream, in the long (54.4 kb) intron between the two alternative exons e2’ and e2, known as the minor bcr (m-bcr). In these circumstances, exons e1’ and e2’ are removed by splicing, and the hybrid BCR-ABL transcript contains an e1a2 junction, and is translated into a smaller 190-kD BCR-ABL fusion protein named p190BCR-ABL. Thus, e14a2 (b3a2) and/or e13a2 (b2a2) fusion transcripts and p210BCR-ABL protein[s] are more characteristic for CML. In contrast, the p190BCR-ABL protein arising from the minor BCR rearrangement producing the e1a2 and/or e1a3 fusion transcript is seen in the majority of cases of Ph+ ALL. Meantime, the expression of e13a2 and/or e14/a2 fusion transcripts is noted in ALL, especially in adult patients [35, 36]. Furthermore, in Ph+ ALL patients some atypical BCR-ABL transcripts, including e1a3, e13a3, and e6a2, have recently been detected [36]. Additionally, occasionally cases of CML with e1a2, e19a1 and e19a2 transcripts [33, 37, 38] have been reported; the clinical significance of which remains unclear.

2.2. Prevalence of BCR-ABL


2.2.1. CML
The vast majority of CML patients have a p210 breakpoint of ABL-BCR gene, and they retain this genotype when their disease progresses to blast crisis (BC). There is also a possibility for coexistent p190 and p210 transcripts in 8% patients with accelerated-phase or BC CML [39].  

It is important to clarify whether the position of the breakpoint within the M-bcr region (5’ M-bcr v 3’ M-bcr), or the type of fusion transcript (for instance, e13a2 v e14a2) somehow influences the disease phenotype or not. The debate has been going on for several years, with some evidence in favor [33, 40, 41] and some against [42, 43] a possible link between M-bcr breakpoint location and disease features, that remains to be cleared up.

Currently many atypical BCR-ABL transcripts are documented in patients with CML, including e1a3, e6a2, e8a2, e13a3, e14a3, e19a2 and others [7, 36, 44]. The most frequent transcripts among them are e6a2 and e1a3 [36]. The clinical course of Ph+ CML with BCR breakpoints outside the above three main cluster regions (e.g. with e1a3) was more benign [45-48], although myeloid BC CML developed in most of them [36, 38, 47, 49]. It has been actively discussed that the poor prognosis of leukemias in the patients with atypical ABL/BCR transcripts might be associated with their lacking the (GET)/Abl-like domain of BCR [50]. This conclusion was based on the findings of a case in Ph-negative CML, where BCR-ABL fusion was recognized by FISH staining of metaphase chromosomes only [51], and wherein e6a2 atypical ABL-BCR fusion, encoding a hybrid p195BCR-ABL protein [50] was detected.

2.2.2. ALL

The BCR-ABL fusion gene is found in around 25% of adult ALL cases [36, 52-54] and in 2% of children [55-56]. Minor breakpoint transcripts (e1a2) encoding for p190 protein, are found in 59% to 70% of positive cases, whereas major breakpoint transcripts (e13a2 or e14a2) encoding for p210 protein are detected in 23% to 30% of cases [57]. Thus, the typical BCR-ABL mRNA transcripts are e1a2, e13a2, and e14a2. At the same time 3% to 19% of ALL patients can express both p210 and p190 fusion transcripts [35, 52-54, 57]. Preliminary data show a high prevalence of p210 copies with respect to copies of the p190 transcript in p190/p210+ cases [35]. Finally, atypical BCR-ABL transcript products are revealed in 1–2% of all Ph+ ALL cases, and include such atypical transcripts as e1a3 (most often), e6a2, e13a3, and e19a2 [7, 36, 58, 59].

The presence of BCR-ABL in ALL is interesting for two reasons. First, the patients with Ph+ ALL have a poor prognosis under conventional therapy [52] and are, therefore, considered high-risk patients and primary candidates for both intensified therapy regimens and alloSCT [36]. Secondly, BCR-ABL positive patients can have a significantly better prognosis under treatment regimens with ABL TKIs such as imatinib [60], dasatinib [61, 62], nilotinib [63] etc., and should take them whenever possible.

2.2.3. Clinical  significance of BCR/ABL isoforms
The majority of BCR-ABL positive adult [52] and childhood ALLs [55, 56, 64] have common or pre-B cell immunological variants with frequent co-expression of CD10, CD13, and CD33 antigens. A special analysis of gene expression patterns showed PILRB, STS-1 and SPRY genes to be overexpressed, whereas TSPAN16 and ADAMTSL4 genes are under-expressed in p190BCR-ABL-positive cases relative to p210BCR-ABL-positive ALLs [54, 57]. No difference was seen in the overall survival of patients with p190BCR-ABL-positive vs p210BCR-ABL-positive ALL. On the basis of this data a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1) has been constructed which, in turn, correlated with overall survival (p=0.0001) in BCR-ABL-positive adult ALL, independent of age (p=0.25) and WBC count at presentation (p=0.003) [54].

The overall response to induction therapy (without TKIs) as well as the type of transplants did not differ significantly between patients with p190+ and p210+ transcripts, although the probabilities of DFS and OS are dependant on BCR/ABL isoforms [35]. Multivariate analysis performed in BCR/ABL+ patients showed that among the variables analyzed (i.e., age, white cell count, expression of CD34, CD10, CD13 and CD33, and type of BCR/ABL transcript), the presence of the p190 fusion transcript was the only powerful independent prognostic factor that favorably influenced disease-free survival (p=0.031) [35]. Besides this, the p190 fusion appears to be the only independent prognostic factor with regard to DFS and OS [35, 65].

2.3. Treatment of BCR-ABL+ leukemias with TKIs

2.3.1. CML
The deregulated tyrosine kinase activity of the BCR-ABL and represents an extremely attractive target for therapeutic intervention. The first original Abl tyrosine kinase inhibitor (TKI) imatinib mesylate (imatinib, IMT) has been developed for clinical use as a result of collaboration between Brian Druker [66-69] and investigators at Ciba-Geigy [70]. Its efficacy was evidenced both on cell lines and the great material collected from patients with CML [69, 71-83]. With a median follow-up of 19 months [77], the estimated rates of complete hematologic remission (CHR) for patients whose initial treatment was imatinib were 96%; major cytogenetic response (MCyR) was 87%; and from CCyR-treated patients, 76%. In patients with accelerated phase CML, imatinib results in a CHR rate of 82% and a MCyR rate of 24% [84]. However, in BC patients CML responses to IMT were of short duration [68, 71], although around 7% patients remain alive after a median observation time of 6 years [85]. In this case imatinib results in a CHR rate of 8–11%, having a MCyR response rate of 16% only, and the median time to relapse in responding patients with BC was about 3 months [86].

The striking efficacy of IMT in CML [25, 72, 74, 75, 78, 79, 87-89] has established this therapy as a new standard for care for the disease. However, resistance is an emerging problem. which has prompted the design of several second-generation TKIs. To overcome the resistance to imatinib [90-93], high-dose IMT therapy was used [94] as well as alternative second-generation TKIs, including dasatinib, nilotinib, INNO-406, MK-0457, and bosutinib (BST).

Dasatinib (BMS-354825; Bristol-Myers Squibb) [68, 92] is active against many of the kinase domain mutants responsible for imatinib resistance [95, 96]. One remarkable exception appears to be the T315I mutation. As shown in a special study of 21 Ph+ patients who failed to respond or relapsed during dasatinib therapy, all patients but one had mutations at residue 315 and/or at residue 317 [30].

Clinical experience in treatment of IMT-resistant or refractory CML patients with dasatinib and nilotinib has been recently reviewed by Goldman [75]. As a result, MHR rates with dasatinib among intolerant or resistant to imatinib patients were 63% for accelerated phase CML (follow-up > or =9 months), 34% for patients with myeloid BC CML, and 35% for those with lymphoid BC CML (follow-up > or =12 months; START-B and START-L trials) [92]. In another study, CHR responses with dasatinib were achieved in 81% IMT-resistant patients with CP CML, while MCyR was demonstrated in 57% of patients [97]. As for high resistance to dasatinib, it was related to the T315I and F317L Abl KD mutations [30, 98, 99].

The next of the second-line BCR-ABL TKI is nilotinib (formerly AMN107), which is 20 to 50 times more active than imatinib against CML cells [87, 93]. The first experience with nilotinib in 119 IMT-resistant patients with CML showed the following. Of 30 patients at BP of the disease, 13 (39%) experienced HR and 9 patients (27%) had a CyR, of whom 6 had a MCyR (Ph+ cells in metaphase, ≤35%). Of 46 patients with accelerated phase CML 33 had a HR and 22 had a CyR. Lastly, 11 of 12 patients with the CP CML had a CHR [90]. As for the resistance to nilotinib, it was again associated with T315I and F317L ABL KD mutation [30] that allows a choice of such TKIs as INNO-406 or MK-0457 for treatment patients with the above unfavorable mutations [30, 75, 98, 99].

2.3.2. ALL

The treatment of Ph+ ALL has also changed dramatically since imatinib was introduced [100-105]. Early phase I and II studies of imatinib in Ph+ ALL revealed its significant, albeit unsustain, activity against relapsed or refractory leukemias [73, 81, 106]. On the other hand, combined with chemotherapy, or even as a single agent, it can produce CR rates of 90% or higher in newly diagnosed patients [6, 85, 100-102, 104, 105, 107-109]. However, these responses were not durable (median, 9 months) [60], whereas further intensification of chemotherapy has had no substantial impact on the unfavorable course of de novo Ph+ adult ALL or in patients who fail first-line therapy [110, 111]. A special study of alternating vs concurrent schedules of imatinib and chemotherapy as front-line for Ph+ ALL demonstrated that co-administration of imatinib and induction cycle 2 results in a CHR rate of 95% and RT-PCR negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (p=0.01). Further, in each cohort, 77% of patients underwent alloHSCT in CR1. As a result, both schedules of imatinib had acceptable levels of toxicity to patients, but concurrent administration of IMT and chemotherapy had resulted greater anti-leukemic efficacy [109].

It should be noted also, that the Ph+ ALL is very characteristic for elderly patients, wherein it has a poor prognosis, with a low CHR rate, high induction mortality, and short remission duration [112]. On the other hand, imatinib as a single agent for elderly patients is toxic enough whereas a potentially curative alloHSCT is not generally applicable [110]. Therefore, it is noteworthy, that the overall CHR rate in the group of elderly patients where imatinib was used for remission induction, was significantly higher (93.5%) than that in patients wherein for induction remission was used multi-agent chemotherapy (50%, p=0.0001) [112].

Despite the similar cytogenetic and molecular characteristics, the resistance to imatinib in patients with Ph+ ALL develops earlier and more frequently than that in CML, and therefore second-line TKIs are necessary. In part, CHR and CyR may be achieved with dasatinib [68, 90], and nilotinib [113], which appear to be ineffective in cases with T315I and F317L KD mutations [99].

Analogous with CML, the best drugs for treatment of patients who seem to be resistant to or intolerant to imatinib, were dasatinib, nilotinib, or bosutinib [6, 63, 91]. According to published data [90, 92], dasatinib induced CHRs in 42% of patients with IMT-resistant Ph+ ALL (follow-up > or =12 months), which is even higher than those in patients with myeloid and lymphoid variants of BC CML.

2.4. BCR-ABL kinase domain (KD) mutations

2.4.1. CML
More than 90 different point mutations encoding for distinct single amino acid substitutions in the BCR-ABL KD have been so far identified, but 10 of them occur in >80% of the cases [20]. The presence of KD mutations has been studied mainly in the advanced phase, and in CP patients when they become resistant to imatinib [113]. Meantime, a special screening for the mutation status of 319 newly-diagnosed patients with CP CML showed the identification of a mutation without other evidence of imatinib resistance to be highly predictive for loss of CCyR (RR, 3.8; p=0.005) and for progression to advanced phase (RR, 2.3; p=0.01). On the basis of this data it was concluded that mutations in the P-loop (excluding residue 244) were associated with a higher risk of progression than mutations elsewhere [114]. Although T315I was the most frequent mutant to emerge, other mutations like T315A, V299L, and F317I were detected that demonstrated retention of sensitivity to imatinib and potentially to nilotinib [30, 115]. Among patients with CP CML who develop (secondary) resistance to imatinib, 30% to 50% have one or more BCR-ABL KD mutations [116-120]. Some DK mutations (V299L, T315I, and F317L/I) were greatly specific for dasatinib [122-125], and others (G250E, Y253H, E255K, T351I, or F311I) for NLT [122] or MK-0457 [126]. Serial investigations showed that the longest period between detection of a mutation and subsequent relapse is observed in patients harboring M351T mutations [125]. In contrast, patients harboring T315I or P-loop mutations demonstrated a 5–25-fold need for immediate withdrawal of imatinib [28, 29].

According to the three largest retrospective studies [28, 117, 127], the incidence of the T315I mutation in IMT-resistant patients was 4%, 11%, and 19%, respectively whereas the frequency of P-loop mutations in the same series of patients was much higher, being 28%, 46%, and 39%, respectively. In general, survival of patients with this mutation remains dependent on the stage of the disease, it having an indolent course in many CP patients [98]. Meantime it is expected that patients with the T315I mutation will also reveal resistance to the treatment with either dasatinib or nilotinib [29, 30, 68, 87, 128]. That is why INNO and ON012380, which are binding regions of BCR-ABL other than the ATP binding pocket, are recommended first of all for these patients [30]. It should be noticed that except for the lack of response to second TKIs (p=0.002), other patient characteristics, including outcomes between patients with T315I and those with other or no mutations were similar.

So the prognostic significance of such KD mutations as T315I, and P-loop region of ABL is undoubted. It is also important that T315I and P-loop mutations were preferentially presented in accelerated phase and of BC CML, compared to other types of mutations in CP CML (p=0.003). In addition, overall survival (OS) after imatiunib initiation was significantly worse for P-loop (28.3 months) and for T315I (12.6 months), than that for other mutations (p=0.0004). Meantime, multivariate analysis of data from CP patients demonstrated a worse OS for P-loop mutations only (p=0.014), but a worse progression-free survival (PFS) for T315I mutations (p=0.014).

The vast number of mutation reports published later have demonstrated number of IMT-resistant patients with different amino acid substitution to be greatly high [89]. Many of these BCR-ABL DK mutations are associated with a relatively modest increase in resistance to imatinib, which may be overcome by dose increase only [30, 51]. On the contrary, mutations such as T315I, and those falling within the P-loop region, i.e., G250E, Y253F/H, and Ee55K/V, confer a highly resistant phenotype [28-30]. An analysis of BCR-ABL mutations by means of denaturating high-performance liquid chromatography found them in 127 of 297 (43%) of the available Ph+ patients. These mutations were revealed in 27% of CP CML patients (14% treated with IMT frontline; 31% treated with IMT post INF-α failure), 52% of accelerated-phase patients, 75% of myeloid BC patients, and 83% of lymphoid BC/Ph+ ALL patients. It should be mentioned that mutations were associated in 30% of patients with primary resistance to imatinib (44% hematologic and 28% cytogenetic), and in 57% of patients with acquired resistance (23% patients who lost CyR; 55% patients who lost HR; and 87% patients who progressed to accelerated phase/BC). On the basis of these findings the following conclusions were drawn. Firstly, amino acid substitution of seven residues (M244V, G250E, V253F/H, E255K/V, T315I, M351T, and F359V) accounts for 85% of all resistance-associated mutations. Secondly, the search for mutations is important both in case of IMT failure and in case of a loss of response at the hematologic or cytogenetic level.

It is interesting to note that in the majority of the resistance patients with CML, mutations were detectable at various intervals prior to hematologic relapse (range 0.9–44.2 months), which was registered at a median of 12.9 months after the start of imatinib therapy. On the other hand, BCR-ABL mutations first became detectable at a median of 5.8 months (range 0–30.5) after commencing imatinib. The difference between time to hematologic relapse and earliest detection of a mutation was highly significant (p<0.0001).

Since BCR-ABL KD mutations in some of CML and Ph+ ALL patients can be found without clinical evidence of resistant disease [26, 129-131], the questions arises as to when tests for DK mutations should be done and by what methods. According to international recommendations, BCR-ABL KD mutation screening in chronic phase CML is only recommended for patients with inadequate initial response to TKIs or those with evidence of loss of response. Mutation screening is also recommended at the time of progression to accelerated or BC CML [26, 132, 133]. Criteria for inadequate initial response (i.e., primary resistance) include lack of CHR, mCyR (66-95% Ph+ metaphases in BM) or lack of MCyR at 3, 6, and 12 months respectively which are similar to the criteria adopted by the European Leukemia Net [89]. Criteria for loss of response to TKI (i.e., secondary resistance) are also based on cytogenetic and/or hematological relapse, with variable use of molecular relapse criteria. One proposed molecular trigger for mutation testing is a tenfold or greater increase in BCR-ABL transcript levels, although smaller rises in BCR-ABL transcript levels may also be predictive of mutation development.

2.4.2. ALL
In comparison with CML, BCR-ABL KD mutations in relapsed Ph+ ALL occur much more frequently (80% to 90% of cases), especially in patients who have been treated with TKIs as initial or ongoing therapy [26, 32, 33, 134].  However, more sensitive detection methods reveal low levels of a point mutation clone in some Ph+ ALL cases before exposure to TKIs. The latter convinces that resistant clones in Ph+ ALL may precede TKI selection [134].

A study of the ABL KD mutation status in newly diagnosed Ph+ ALL patients showed that IMT-resistant TK domain mutations were detected in 38% patients even before exposure to IMT. Although the frequency of the mutant allele was low in such patients at the time of relapse, the same mutation was present as the dominant clone in 90% of the relapsing cases [134].

2.5. Hematopoietic stem cell transplantation (HSCT)

2.5.1. CML
Until the advent of imatinib, alloHSCT was considered to be the only known curative therapy for patients younger than 50 years having suitable HLA-identical siblings, HLA-matched family members, or HLA-matched volunteer unrelated donors [75]. Although the morbidity and indeed mortality attributable to the procedure were both appreciable, the probability of survival could be predicted with reasonable accuracy via the scoring system developed for the European Group for Blood and Marrow Transplantation (EBMT) [135]. Graft-versus-leukemia (GvL) effects contribute substantially to the curative potential of this approach [25, 136]. However, relapse occurs in approximately 5% to 20% of patients transplanted in chronic phase. While some patients remain in a stable MRD status, others rapidly progress to overt clinical relapse [137]. In order to re-induce MolR through augmenting or re-establishing the GvL effect, cessation of immunosuppression [138] and, particularly, donor lymphocyte infusion (DLI) are standard approaches for patients with relapse after alloHSCT [139, 140]. Unfortunately, this approach is frequently associated with substantial risk, mainly induction of graft-versus-host disease (GvHD) or BM suppression [139-144], which in large surveys have been observed in approximately 48% and 18% of patients [25, 145]. As a result, over 80% of patients with low risk of GvHD (i.e., 0–2) had a probability of being alive at 5 years [146] and the probability of subsequent relapse for patients free of detectable CML was extremely low [147].

Although the treatment with imatinib is less toxic, it may not cure the disease and, being used for a long time makes it very expensive. Additionally, resistance to imatinib can also occur in the course of the therapy. Therefore, alloHSCT for the treatment of some CML patients remains  necessary [25]. Firstly, transplanted HSC have anti-leukemic activity and contribute to maintaining remissions. Secondly, the effect of imatinib may be increased by potential side effects of DLI and vice versa [148]. Since suppression of MRD with imatinib can theoretically allow re-establishment of complete chimerism as well as restore full GvL effects, this approach has been recently tested successfully in clinical practice [37, 77, 149]. Additionally, a special molecular investigation showed that 70% of patients with CML who relapsed after alloHSCT can achieve CMolR after imatinib treatment and DLI [139, 140, 142, 148].

2.5.2.  ALL
The poor outcome with conventional chemotherapy made alloHSCT an attractive option for patients with Ph+ ALL [100, 101, 108, 109, 150-157]. The first study of allo BMT in 10 patients with Ph+ showed that 4 patients died of transplant-related complications, while 6 patients survived the transplant and remained in CR (median follow-up; 19 months) [158]. A retrospective analysis in 67 Ph+ ALL patients aged 5–49 years who underwent alloHSCT, showed that 21 of them (31%) were in continuous CR≥2 years after transplant [159]. There were no significant differences in TRM, DFS, and relapse rate between patients who had been transplanted in first or later CR. However, 2-year DFS was much lower in patients who had never achieved CR before transplant. Better results were reported later [151, 154, 160, 161]. For instance, Snyder et al [151] reported a 65% DFS rate (15/23) at 3 year post-transplant, whereas the estimated relapse rate during that period was only 12%. According to data from the French Bone Marrow Transplantation Society [162], in a study where 76 adult patients were in CR1 at the time of transplant, 2-year OS was demonstrated in 50% of patients, whereas the 2-year relapse incidence rate was 37%. In the largest prospective alloHSCT study (conducted during the pre IMT era), 5-year OS was superior in those who underwent MRD alloHSCT compared with chemotherapy or autologous HSCT [163, 164]. Unfortunately, despite its efficacy, currently only 20% to 60% of patients actually undergo alloHSCT. Moreover, even after alloHSCT in CR1 the probability of relapse for Ph+ ALL patients is approximately 30%, which together with a high transplant-related mortality of 20% to 40% highlights the limitations of current therapy [109, 165, 166].

The recent appearance of TKIs in clinical practice has changed the up-front treatment paradigm and appears to affect the outcome after HCST [167]. In contrast with CML, wherein TKIs have changed our attitude to HSCT as the treatment of first choice [168], TKIs in Ph+ ALL appear to be seen only as a “bridge to transplant”, helping more patients to achieve and maintain sufficiently durable remission before [156] or after [63] HSCT. The latter is desirable to undergo in CR1. In such a case the long-term survival rates may be greater than 35%. Furthermore, the results can be essentially improved after first-line imatinib interim treatment [107, 157]. The data suggests that the 3-year estimated probabilities of relapse, DFS, and OS were 3.5% vs 47.3% in controls (p=0.02), and 78.1% vs 38% in controls (p=0.001), respectively, without much difference in the transplant-related toxicities. In this context, other studies have also demonstrated the feasibility of giving imatinib following alloHSCT for BCR-ABL+ ALL either preemptively or to treat any MRD detected after transplant prior to relapse instead of using a donor lymphocyte infusion [169, 170]. The management of patients with Ph+ ALL relapsing after alloHSCT represents a major challenge with limited chances of success. The efficacy of DLI in Ph+ ALL is much lower that that in CML [171], which is explained by the diverse immune escape mechanisms of ALL blasts from GVL effects of DLI [172]. On the other hand, the addition of cytoreductive chemotherapy to DLI does not seem to improve the outcome of relapsed ALL patients [173], whereas  a combination of TKIs and DLI may be greatly effective [63].

2.6. Monitoring treatment and/or minimal residual disease

2.6.1. CML

2.6.1.1. Blood counts and bone marrow karyotyping

Complete blood counts should be performed at least weekly until they have stabilized, with greater intervals thereafter. Once CHR has been documented, monitoring continues with karyotyping of bone marrow metaphases, which is recommended at 6, 12, and 18 months, or until CCyR has been achieved [38, 89, 174, 175]. If there are fewer than 20 metaphases, the cytogenetic response can be validated by determining the level of BCR-ABL transcripts and by molecular cytogenetics, or FISH. Of note is that FISH can be performed on metaphases or more frequently and more conveniently on interphase cells (IP-FISH) [38, 176]. In fact, all FISH data correlates very significantly with chromosome banding data [177], as well as with BCR-ABL transcript levels [176, 177]. Moreover, FISH can detect deletions of the long arm of chromosome 9 and variant translocations.

2.6.1.2.  Monitoring BCR-ABL transcript levels
Molecular monitoring of BCR-ABL transcript levels with RQ-PCR has become an integral part of management of patients with CML [132, 178-180]. This is particularly relevant in the era of imatinib therapy, when residual levels of leukemia usually fall below the level of detection via bone marrow cytogenetic analysis. Indeed, even small increases in the BCR-ABL level can identify patients with TK domain mutations that lead to IMT resistance.

Currently, the best molecular approach for monitoring BCR-ABL transcript levels is considered to be RQ-PCR [133, 178, 179]. The best gene for internal reference appears to be β-glucuronidase and not the widely-used ABL gene [180]. In fact, a failure to achieve a major MolR by 18 months after starting imatinib therapy is considered a suboptimal response requiring careful re-evaluation and possible reassessment of therapy [92]. Various prerequisites for achieving optimal sensitivity and standardization have been agreed upon and published [133, 181, 182]. According to recent international reporting scale, major MolR is established at BCR-ABL 0.1%, whereas a value of 1.0% is approximately equivalent to the achievement of CCyR  [38].  From a practical point of view, it has been suggested that RQ-PCR must be performed every 3 months even in patients who achieve a MolR [179]. If, after alloHSCT, the attainment of BCR-ABL-negative status is conferred, the overall survival is significantly improved (57% vs 12%; p=0.006) [176]. In contrast, in the case where BCR-ABL levels increase, there is the possibility of identifying the patients who do not respond properly to the proposed therapy or even to start the search for BCR-ABL mutations [183, 184]. However, even considering that RQ-PCR is fundamental for monitoring patients with CCyR, there are other reasons to suggest that cytogenetics should not be completely replaced by RQ-PCR in the follow-up of CML patients. Firstly, additional chromosome abnormalities present at diagnosis or arising during the disease may have a prognostic influence [183]. Secondly, there is evidence of clonal cytogenetic abnormalities in the Ph-negative cells [185, 186] which appeared after suppression of Ph-positive clone by imatinib and, in a majority of cases, could be a characteristic of future myelodysplasias [38]

2.6.1.3. Monitoring BCR-ABL kinase domain mutations
A mutation at the TK domain of the oncogenic BCR-ABL protein is frequently detected in patients with CML who fail to respond to TKIs or lose the response [187>]. The best approach for screening for BCR-ABL mutations during therapy with TKIs is D-HPLC [28, 31]. The studies show that mutations may be detectable several months before relapse, but the occurrence of BCR-ABL mutations during imatinib therapy is predictive of relapse.
     
2.6.2. ALL

2.6.2.1. Cytogenetic monitoring

In contrast to CML, cytogenetic changes in Ph+ ALL in the course of chemotherapy do not last long. Therefore, the main tasks of cytogenetics, including FISH, in these patients are: a) to verify a CCyR; or, in turn, b) to detect a resistance to chemotherapy, TKI or HSCT.

2.6.2.2. BCR-ABL transcript level monitoring
BCR-ABL RNA transcripts are suitable molecular markers for MRD analysis and for guiding therapy [25, 188, 189]. However, MRD analysis with RT-PCR is affected by intra- and inter-assay variability, which appear to reflect different proportions of leukemic blast cells. A special investigation of samples from 56 patients showed levels of BCR-ABL to be higher in bone marrow than in peripheral blood. In fact, they did not differ when normalized to 100% blasts. Moreover, the numbers of BCR-ABL transcripts per blast in 25 sequential BM and 8 sequential PB did not change significantly during evolution of Ph+ ALL. As for the mean number of p210 copies per blast concern they were 1.1 log higher than that for p190 (p=0.0006).

2.6.2.3. BCR-ABL kinase domain mutation monitoring
In contrast to CML, pre-existence of mutations including the T315I mutation did not adversely effect either the CR rate following imatinib or chemotherapy induction or the achievement of BCR-ABL negativity in response to combination therapy, when compared with patients exhibiting only non-mutated BCR-ABL at diagnosis [190]. In our opinion, this might be explained by the earlier use of high-doses chemotherapy followed by alloHSCT.

2.7. Prognosis

2.7.1. CML
In the TKI era the prognosis for CML patients has greatly improved. The majority of patients can now expect to survive 10 to 20 years [74, 88, 191]. It is even possible that some patients treated for a number of years can stop the imatinib and be regarded as cured of their leukemia [192]. Hence, any possibility of recognizing the minority of patients who respond poorly to imatinib at the earliest opportunity is very important [193]. Therefore, a series of empirical recommendations developed on behalf of the European LeukemiaNet (Table 1) [89] are used by clinicians to identify those CP CML patients responding poorly to imatinib at standard dosage. As for the other prognostically poor and verified factors in CML patients, they include the following: a) age; b) advanced stages CML; and c) BCR-ABL domain mutations, mainly, T315I.

Table 1. Modified European LeukemiaNet definition of failure and suboptimal response for previously untreated, early CP CML patients treated with 400 mg IMT daily
Failure implies that the patient should be moved to other treatments whenever available; NA indicates not applicable; HR, hematological response; CHR, complete HR; CyR, cytogenetic response; CCyR, complete CyR; MMolR, major molecular response; ACA, additional chromosome aberrations, and TK tyrosine kinase

Time Failure Suboptimal response Warnings
Diagnosis NA NA High risk
      del 9q+; addit chrom abnormalities (ACA) in Ph+ cells
3 months No HR Less than CHR  
6 months Less than CHR Less than partial CyR (Ph+ >35%)  
12 months Less than partial CyR (Ph+ >35%) Less than CCyR Less than MMolR
18 months Less than CCyR Less than MMolR  
At any time Loss of CHR; loss of CCyR; TK domain mutation ACA in Ph+ cells; Loss of MMolR; TK domain mutation Any rise in transcript level; ACA in Ph- cells

2.7.2. ALL
The prognosis of Ph+ ALL – whatever the fusion protein – is poor in both adults and children [70, 194]. Detailed analysis of prognostic-related factors showed that deletion of the IKZF1 gene [195-199], as well as the secondary chromosome aberrations at diagnosis [200-204], in addition to t(9;22), had a significant association with shorter RFS. The latter has been reported in both before the imatinib [177, 178] ] and during the imatinib era [21]. Partly, there is data from 80 Ph+ ALL patients treated with imatinib, which was followed by alloHSCT in 60 of them. In fact it was found that the 2-year RFS for those who had undergone alloHSCT during CR1 was 62.6±7.5% compared to 62.1±12.3% for those who had not undergone alloHSCT. When alloHSCT was considered as a time-dependent covariant, it was shown to have no significant effect on RFS. On the other hand, a statistically significant negative impact on RFS for +der(22)t(9;22) and 9p abnormalities (p<0.001 and p<0.005) [21] was revealed, although it had not been demonstrated earlier [204].

Conclusions and future directions

The study of patients with Ph+ leukemias allowed a clarification of many sides of the nature and pathogenesis of leukemias [127, 128], and helped to develop new therapeutic approaches [208, 209]. The treatment of these disorders was partly revolutionized with TKIs. As a result, nowadays the vast majority of the patients with CML can be treated without alloHSCT. As far as HSCT is concerned, this must be reserved for those CML patients who become resistant to TKIs. The main reason for the resistance formation appears is considered to be mutations of BCR-ABL KD, primarily T315I. For achieving effect in relapsed after HSCT patients may be effectively used DLI which is the ideal approach for treating these CML patients [164].

In contrast to CML, alloHSCT is the only known curative modality for patients with Ph+ ALL under 55 years old. Naturally, it must be coupled by high dose chemotherapy and TKIs before transplantation [157, 170]. If such therapy is unsuccessful, testing for BCR-ABL domain mutations is necessary. Besides other prognostic factors, the following are considered to be important: a) additional chromosome changes, including the 2nd Ph-chromosome and 9p abnormalities; b) deletion of genes (i.e., IKAROS) needed for natural differentiation of B-cells; c) some cryptic chromosome changes; and d) micro-deletions of many important genes, which respond for natural differentiation of lymphoid and myeloid hematopoietic cells. The latest  investigations appear to be directed onto: a) the development of new techniques of mutation status testing;  b) the active introduction into clinical practice of TKIs of second- and third-lines; c) the further elucidation of mutated genes’ participation in both pathogenesis and resistance formation to treatment of Ph+ leukemias. As a result, one can expect that discoveries in these regions will allow the development of a concepts for target therapy of Ph+ leukemias, enabling more effective treatment than ever before.

References

1. Nowell PC, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497-9.

2. Rowley JD. Letter: A new consistent chromosome abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290-3.

3. Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96:3343-56.

4. Advani AS, Penderqast AM. Bcr-Abl variants: Biological and clinical aspects. Leuk Res. 2002;26:713-20. doi: 10.1016/S0145-2126(01)00197-7.

5. Pane F, Intrieri M, Quintarelli C, et al. BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations. Oncogene. 2002;21:8652-67.

6. Ottmann O, Dombret H,  Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007;110:2309-15. doi: 10.1182/blood-2007-02-073528.

7. Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.  Blood. 1996;88:2375-84.

8. Secker-Walker LM, Morgan GJ, Min T, et al. Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophils. Report of two cases. Cancer Genet Cytogenet. 1992;58:29-34. doi:10.1016/j.leukres.2005.06.003.

9. Alimena G, Cedrone M, Nanni M, et al. Acute leukemia presenting a variant Ph chromosome with p190 expression, dup 3q and -7, developed after malignant lymphoma treated with alkilating agents and topoisomerase II inhibitors. Leukemia. 1995;9:1483-6. pmid: 7658716.

10. Mitani K, Sato Y, Tojo A, et al. Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein. Br J Haematol. 1990;76:221-5. pmid: 2094324.

11. Martiat P, Meccucci C, Nizet Y, et al. P190 BCR/ABL transcript in a case of Philadelphia-positive multiple myeloma. Leukemia. 1990;4:751-4. pmid: 2232886.

12. Verhoef G, Meens P, Stul M, et al. Cytogenetic and molecular studies of the Philadelphia translocation in myelodysplastic syndrome. Report of two cases and review of the literature. Cancer Genet Cytogenet. 1992;59:161-6.

13. Keung YK, Beaty M, Powell BL, et al. Philadelphia chromosome positive myelodysplastic syndrome and acute myeloid leukemia – retrospective study and review of literature. Leuk Res. 2004;28:579-86. doi: 10.1016/j.leukres.2003.10.027.

14. Stoll DB, Peterson P, Exten R, et al. Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome. Am J Hematol. 1988;27:77-83. pmid: 3422539.

15. Martiat P, Ifrah N, Rassool F, et al. Molecular analysis of Philadelphia positive essential thrombocythemia. Leukemia. 1989;3:563-5. pmid: 2747291.

16. Cervantes F, Urbano Ispizua A, Villamor N, et al. Ph-positive chronic myeloid leukemia mimicking essential thrombocythemia and terminating into megakaryoblastic blast crisis: Report of two cases with molecular studies. Leukemia. 1993;7:327-30. pmid: 8426485.

17. Pane F, Frigeri F, Sindona M, et al. Neutrophilic-chronic myelogenous leukemia: A distinct disease with a specific molecular marker (BCR-ABL with c3a2 junction). Blood. 1996;88:2410-4.

18. Dorshkind K, Witte ON. Linking the hematopoietic microenvironment to imatinib-resistant Ph+ B-ALL. Genes Dev. 2007;21:2249-52. doi: 10.1101/gad.1600307.

19. Piccaluga PP, Paolini S, Martinelli G. Tyrosine kinase inhibitors for the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Cancer. 2007;110:1178-86. doi: 10.1002/cncr.22881.

20. Melo JV, Chuah C. Novel agents in CML therapy: tyrosine kinase inhibitors and beyond. Hematology Am Soc Hematol Educ Program. 2008;427-35.

21. Yanada M, Takeuchi J, Sugiura I, et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica. 2008;93:287-90. doi:10.3324/haematol.11891.

22. Nashed AL, Rao KW, Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagnostics. 2003;5:63-72.

23. Qiu H, Miao K, Wang R, et al.  The application of fluorescence in situ hybridization in detecting chronic myeloid leukemia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009;26:207-10. Chinese. pmid: 19350518.

24. Virgili A, Brazma D, Reid A, et al. FISH mapping of Philadelphia negative BCR/ABL I positive CML. Mol Cytogenetics. 2008;1:755-8. doi: 10.1186/1755-8166-1-14.

25. Hardling M, Wei Y, Palmqvist L, et al.  Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate. Med Oncol. 2004;21:349-58. doi: 10.1385/MO:21:4:349.

26. Doi Y, Sasaki D, Terada C, et al. High-resolution melting analysis for a reliable and two-step scanning of mutations in the tyrosine kinase domain of the chimerical bcr-abl gene. Int J Hematol. 2009 May 23. [Epub ahead of print]. doi: 10.1007/s12185-009-0337-y.

27. Jones D, Kamel-Reid S, Bahler D, et al. Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia. A report of the association for molecular pathology. J Mol Diagnostics. 2009;11:4-11. pmid: 19095773.

28. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12:7374-9. doi: 10.1158/1078-0432.CCR-06-1516.

29. Soverini S, Colarossi S, Gnani A, et al. Resistance to dasatinib in Philadelphia-positive leukemia patients is mainly mediated by the presence or the selection of mutations at residues 315 and 317 in the Bcr-Abl kinase domain. Haematologica. 2007;109:401-4. doi: 10.3324/haematol.10822.

30. Soverini S, Iacobucci I, Baccarani M, and Martinelli G. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. Haematologica. 2007;92:437-9. doi: 10.3324/haematol.11248.

31. Ernst T, Erben P, Miller M, et al. Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib. Haematologica. 2008;93:186-92. doi: 10.3324/haematol.11993.

32. Jones D, Thomas D, Yin CC, et al. Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors. Cancer. 2008;113:985-94.

33. Jones D, Luthra R, Cortes J, et al.  BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome–positive leukemias. Blood. 2008;112:5190-2. pmid: 18809762.

34. Yeoh EJ, Ross ME, Shurtleff SA, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1:133-43. doi: 10.1016/S1535-6108(02)00032-6.

35. Cimino G, Pane F, Elia M, et al. The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. Haematologica. 2006;91:377-80.

36. Burmeister T, Schwartz S, Taubald A, et al. Atypical BCR-ABL mRNA transcripts in adult acute lymphoblastic leukemia. Haematologica. 2007;92:1699-702. doi: 10.3324/haematol.11737.

37. Ohsaka A, Shina S, Kobayashi M, et al. Philadelphia chromosome-positive chronic myeloid leukemia expressing p190(BCR-ABL). Intern Med. 2002;41:1183-7.

38. Jiang DZ, Chen ZM, Lou JY, et al. Cytogenetic and molecular analysis of 1193 cases with chronic myeloid leukemia Zhonghua Xue Ye Xue Za Zhi. 2007;28:1-5. Сhinese. pmid: 17649716.

39. Dhingra K, Talpaz M, Kantarjian H, et al. Appearance of acute leukemia-associated P190 BCR-ABL in chronic myelogenous leukemia may correlate with disease progression. Leukemia. 1991;5:191-5. pmid: 2013978.

40. Melo JV, Myint H, Galton DA., and Goldman JM.  P190BCR-ABL chronic myeloid leukemia: The missing link with chronic myelomonocytic leukemia? Leukemia. 1994;8:208-11. pmid: 8289491.

41. Elliott SL, Taylor KM, Taylor DL, et al. Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location. Leukemia. 1995;9:946-50. pmid: 7596182.

42. Shepherd P, Suffolk R, Halsey J, et al. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukemia: No correlation with clinical features, cytogenetic response, duration of chronic phase or survival. Br J Haematol. 1995;89:546-54. pmid: 7734353.

43. Rozman C, Urbano Ispizua A, Cervantes F, et al. Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia. Leukemia. 1995;9:1104-7. pmid: 7596178.

44. Kutsev S, Velchenko M. The role of BCR-ABL gene mutation analysis in the optimization of target therapy of chronic myeloid leukemia. Clin Oncohematol. 2008;1:190-9. Russian.

45. Al-Ali HK, Leiblein S, Kovacs I, et al. CML with an e1a3 BCR-ABL fusion: rare, benign, and a potential diagnostic pitfall. Blood. 2002;100:1092-3.

46. Snyder DS, McMahon R, Cohen SR, et al. Chronic myeloid leukemia with an e13a3 BCR-ABL fusion: benign course responsive to imatinib with an RT-PCR advisory. Am J Hematol. 2004;75:92-5. doi: 10.1002/ajh.10456.

47. Lee JJ, Kim HJ, Lee S, et al. Imatinib induces a cytogenetic response in blast crisis of interferon failure chronic myeloid leukemia patients with e19a2 BCR-ABL transcripts. Leukemia. 2004;18:1539-40. doi: 10.1038/sj.leu.2403454.

48. Popovici C, Cailleres S, David M, et al. E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib. Leuk Lymphoma. 2005;46:1375-7. doi: 10.1080/10428190500138138.

49. Grégoire M-J, Latger-Cannard V, Staal A, et al. Identification of an acute basophilic leukemia carrying a rare e6a2 BCR-ABL transcript. Acta Haematol. 2006;116;216-8. doi: 10.1159/000094686.

50. Colla S, Sammarelli G, Voltorini S, et al. e6a2 BCR-ABL transcript in chronic myeloid leukemia: is it associated with aggressive disease? Haematologica. 2004;89:611-3.

51. Hochhaus A, Reiter A, Sklandy H, et al. A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome negative chronic myelogenous leukemia. Blood. 1996;88:2236-40.

52. Gleiβner B, Gökbuget N, Bartram CR, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002;99:1536–43.

53. Elia LI, Manchini M, Moleti L, et al. A multiplex reverse transcriptase-polymerase chain reaction strategy for the diagnostic molecular screening of chimeric genes: a clinical evaluation on 170 patients with acute lymphoblastic leukemia. Haematologica. 2003;88:275-9.

54. Juric D, Lacayo NJ, Ramsey MC, et al. Differential gene expression patterns and interaction networks in BCR-ABL-positive and –negative adult acute lymphoblastic leukemias. J Clin Oncol. 2007;25:1341-9. doi: 10.1200/JCO.2006.09.3534.

55. Schlieben S, Borkhardt A, Reinisch I, et al. Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05–92. Leukemia. 1996;10:957-63. pmid: 8667652.

56. Uckun FM, Nachman JB, Sather HN, et al. Clinical significance of Philadelphia chromosome-positive pediatric acute lymphoblastic leukemia in context of contemporary intensive therapies: a report from the children’s cancer group. Cancer. 1998;83:2030–9. doi: 10.1002/(SICI)1097-0142(19981101)83:9<2030::AID-CNCR21>3.0.CO;2-Q.

57. Scheuring US, Pfeifer H, Wassmann B, et al. Methodologic and biological variability of quantitative real-time polymerase chain reaction analysis of Bcr-Abl expression in Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2003;88:1074-5.

58. Rotoli B, Pane F, Salvatore F, et al. The e19a2 bcr/abl breakpoint in acute lymphoblastic leukemia. Br J Haematol. 2000;110:493-6.

59. Wilson GA, Van den Berghe EA, Politt RC, et al. Are aberrant BCR-ABL transcripts more common than previously thought? Br J Hematol. 2000;111:1109-11.

60. Wassmann B, Gökbuget N, Scheuring UJ, et al. A randomized multicenter open label phase II study to determine the safety and efficacy of induction therapy with imatinib (Glivec, formerly STI571) in comparison with standard induction chemotherapy in elderly (>55 years) patients with Philadelphia chromosome-positive (Ph+/BCR-ABL+) acute lymphoblastic leukemia (ALL) (CSTI571ADE10). Ann Hematol. 2003;82:716-20.

61. Talpaz M, Shah N, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia-chromosome-positive leukemias. N Engl J Med. 2006;354:2531-41.

62. Volkova MA. New possibilities in the therapy of the chronic myelocytic leukemia: dasatinib. Clin Onkohematol. 2008;1:218-26. Russian.

63. Tiribelli M, Sperotto A, Candoni A, et al. Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leukemia Res. 2009;33:174-7.

64. Schultz KR, Pullen DJ, Sather HN, et al. Risk and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG). Blood. 2007;109: 926-35. doi: 10.1182/blood-2006-01-024729.

65. Secker-Walker LM, Craig JM. Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review. Leukemia. 1993;7:147–51. pmid: 8426467.

66. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of BCR-ABL positive cells. Nat Med. 1996;2:561-6. pmid: 8616716.

67. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New Engl J Med. 2001;344:1031-7.

68. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-42.

69. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of imatinib therapy for newly diagnosed chronic leukemia in chronic-phase shows sustained responses and high overall survival. N Engl J Med. 2006;355:2408-17.

70. Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood. 2007;110:2828-37. doi: 10.1182/blood-2007-04-038943.

71. Kantarjian HM, Cortes J, O’Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome positive chronic myelogenous leukemia in blast phase. Blood. 2002;99:3547-53.

72. Kantarjian HM, O’Brien S, Cortes JE, et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood. 2002;100:1590-5.

73. Kantarjian HM, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2003;346:645-52.

74. Kantarjian HM, Talpaz M, O’Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101:473-5. doi: 10.1182/blood-2002-05-1451.

75. Kantarjian HM, Talpaz M, O’Brien S, et al. Survival benefit with imatinib mesylate versus-interferon alfa-based regimens in newly diagnosed chronic phase chronic myelogenous leukemia. Blood. 2006a;108:1835-40.

76. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100:1965-71. doi: 10.1182/blood-2001-12-0181.

77. Radojkovic M, Ristic S, Pavlovic S, Colovic M. Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis. Leuk Res. 2009;33:10-2. doi: 10.1016/j.leukres.2008.10.028.

78. Roy L, Guilhot J, Krahnke T, et al. Survival advantage with imatinib compared to the combination interferon-α plus cytarabine in chronic phase CML: historical comparison between two phases III trials. Blood. 2006;108:1478-84. doi: 10.1182/blood-2006-02-001495.

79. de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood. 2007;109:1408-13. doi: 10.1182/blood-2006-03-011908.

80. Vignetti M, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) LAL201-B protocol. Blood. 2007;109:3676-8. doi: 10.1182/blood-2006-10-052746.

81. Zaritsky AYu, Lomaia EG, Vinogradova OYu, et al. Prognosis factors in Imatinib mesylate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia. Ther Arkh. 2007;79(8):17-22. Russian.

82. Palandri F, Iacobucci I, Martinelli G, et al. Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, Philadelphia-positive chronic myeloid leukemia: The GIMENA Working Party on CML. J Clin Oncol. 2008;26:106-11. doi:  10.1200/JCO.2007.13.2373.

83. Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112:4808-17.

84. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928-37.

85. Palandri F, Castagnetti F, Testoni N, et al. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. Haematologica. 2008;93:1792-6. doi: 10.3324/haematol.13068.

86. Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99:3530-9.

87. Kantarjian HM, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354:2542-51.

88. De Lavallade H, Apperley JF, Khorashad JK, et al. Imatinib for newly diagnose patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358-63.

89. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the managements of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809-20. doi: 10.1182/blood-2006-02-005686.

90. Brave M, Goodman V, dvardas Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res. 2008;14:352-9. doi: 10.1158/1078-0432.CCR-07-4175.

91. Steinberg M. Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther. 2007;29:2289-308. doi: 10.1016/j.clinthera.2007.11.005.

92. Keam SJ. Dasatinib: in chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. BioDrugs. 2008;22:59-69. pmid: 18215092.

93. Le Coutre P, Ottmann OG, Giles F, et al. Nilotinib (formally AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008;111:1834-9. doi: 10.1182/blood-2007-04-083196.

94. Castagnetti F, Palandri F, Amabile M, et al. Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party. Blood. 2009;113:3428-34. doi: 10.1182/blood-2007-08-103499.

95. Palandri F, Castagnetti F, Alimena G, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up. Haematologica. 2009;94:205-212. doi: 10.3324/haematol.13529.

96. Tokarski JS, Newitt JA, Cheng CY, et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res. 2006;66:5790-7. 97. Guilhot F, Apperley J, Kim D-W, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or- intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143-50.

97. Guilhot F, Apperley J, Kim D-W, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or- intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143-50. doi: 10.1182/blood-2006-09-046839.

98. Jabbour E, Kantarjian H, Jones D, et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood. 2008;112:53-5. doi: 10.1182/blood-2007-11-123950.

99. Jabbour E, Kantarjian HM, Jones D, et al.  Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after  therapy with tyrosine kinase inhibitors. Blood. 2008;112:4839-42. doi: 10.1182/blood-2008-04-149948.

100. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004; 103:4396-407. doi: 10.1182/blood-2003-08-2958.

101. Thomas D.A. Philadelphia chromosome–positive acute lymphocytic leukemia: a new era of challenges. Hematology Am Soc Hematol Educ Program Book. 2007:435-43.

102. Towatari M, Yanada M, Usui N, et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood. 2004;104:3507-12. doi: 10.1182/blood-2004-04-1389.

103. Ottmann OG, Wassmann B. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology. Am Soc Hematol Educ Program. 2005:118-22.

104. Yanada M, Naoe T. Imatinib combined chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: major challenges in current practice. Leuk Lymphoma. 2006;47:1474-53. doi: 10.1080/10428190600634085.

105. Yanada M, Takeuchi J, Sugiura I, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24:460-6.

106. Wassmann B, Pfeifer H, Scheuring UJ, et al. Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with imatinib. Blood. 2004;103:1495-8. doi: 10.1182/blood-2003-01-0154.

107. Lee S, Kim Y-J, Min C-K, et al.  The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2005;105:3449-57. doi: 10.1182/blood-2004-09-3785.

108. Wassmann B, Pfeifer H, Stadier M, et al. Early molecular response to post transplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005;106:458-63. doi: 10.1182/blood-2004-05-1746.

109. Wassmann B, Pfeifer H, Gökbuget N, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2006;108:1469-77. doi: 10.1182/blood-2005-11-4386.

110. Ohno R. Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Curr Oncol Rep. 2008;10:379-87. pmid: 18706265.

111. Scheuring US, Pfeifer H, Wassmann B, et al. Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571). Blood. 2003;101:85-90. doi: 10.1182/blood-2002-02-0360.

112. Ottmann OG, Wassmann B, Pfeifer H, et al. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2007;109:2068-76.

113. Apperley JF. Mechanisms of resistance to imatinib in chronic myeloid leukemia. Part I. Lancet Oncol. 2007;8:1018-29. pmid: 17976612.

114. Khorashad JS, de Lavallade H, Apperley JF, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008;26:4806-13. pmid: 18645191.

115. Saglio G, Ulishiani S, Bosa M, et al. New therapeutic approaches and prognostic factors in chronic myeloid leukemia. Leuk Lymphoma. 2008;49:625-8. doi: 10.1080/10428190801896210.

116. Verma D, Fava C, Kantarjian H, Cortes J. Complexity of BCR-ABL kinase domain mutations during the course of therapy with tyrosine kinase inhibitors in chronic myeloid leukemia. Am J Hematol. 2009;84:256-7. doi: 10.1002/ajh.21366.

117. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20:1767-73. doi: 10.1038/sj.leu.2404318.

118. Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program. 2007:376-83.

119. Al-Ali HK, Heinrich MC, Lange T, et al.  High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J. 2004;5:55-60.

120. Lahaye T, Riehm B, Berger U, et al.  Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer. 2005;103:1659-69. doi: 10.1002/cncr.20922.

121. Quintas-Cardama A, Kantarjian H, Jones D, et al. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood. 2007;109:497-9. doi: 10.1182/blood-2006-07-035493.

122. Cortes J, Rousselot P, Kim D, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:3207-13. doi: 10.1182/blood-2006-09-046888.

123. Shah NP, Skaggs BJ, Branford S, et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J Clin Invest. 2007;117:2562-9. doi: 10.1172/JCI30890.

124. Soverini S, Martinelli G, Colarossi S, et al. Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL. Lancet Oncol. 2007;8:273-4. doi: 10.1016/S1470-2045(07)70078-5.

125. Jabbour E, Kantarjian HM, Jones D, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood. 2008;112:4839-42. doi: 10.1182/blood-2008-04-149948.

126. Giles FJ, Cortes J, Jones D, et al. VK-047, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood. 2007;109:500-2. doi: 10.1182/blood-2006-05-025049.

127. Nicolini FE, Corm S, Lĕ QH, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia. 2006;20:1061-6. doi: 10.1038/sj.leu.2404236.

128. Hochhaus A, Kantarjian H, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic- phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109:2303-9. doi: 10.1182/blood-2006-09-047266.

129. Zonder JA, Pemberton P, Brandt H, et al. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to imatinib treatment. Clin Cancer Res. 2003;9:2092-7.

130. Chu S, Xu H, Snyder DS, et al. Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood. 2005;105:2093-8. doi: 10.1182/blood-2004-03-1114.

131. Sherbenou DW, Wong MJ, Humayun A, et al. Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic responses to imatinib. Leukemia. 2007;21:489-93.

132. Hughes T. ABL kinase inhibitor therapy for CML: baseline assessments and response monitoring. Hematology Am Soc Hematol Educ Program Book. 2006:211-8.

133. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28-37. doi: 10.1182/blood-2006-01-0092.

134. Pfeifer H, Wassmann B, Pavlova A, et al. Kinase domain mutations of BCR-ABL frequency precede Imatinib-based therapy and give to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2007;110:727-34. doi: 10.1182/blood-2006-11-052373.

135. Passweg JR, Walker I, Sobocinski KA, et al. Validation and extension of the EBMT risk score for patients with chronic myeloid leukemia (CML) receiving allogeneic haemopoietic stem cell transplants. Br J Haematol. 2004;125:613-20.

136. Sullivan KM, Weiden PL, Storb R, et al.  Influence of acute and chronic graft-versus-host disease on relapse and survival after bone transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.  Blood. 1989;73:1720-8.

137. Serrano J, Roman J, Sanchez J, et al.  Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210 (BCR-ABL) and p190 (BCRABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190 (BCR- ABL) detection precedes cytogenetic relapse. Blood. 2000;95:2659–65.

138. Collins RH, Roggers ZR, Bennett M, et al. Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: Apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant. 1992;10:391-5. pmid: 1422499.

139. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood. 1995;86:2041-50.

140. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371-83.

141. Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes  for relapse of chronic myeloid leukemia after bone marrow transplantation: Separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 1995;86:1261-8.

142. Collins RH, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433-44. pmid: 9053463.

143. Dazzi F, Szydio RM, Goldman JM. Donor lymphocyte infusion for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: Where we now stand. Exp Hematol. 1999;27:1477-86.

144. Dazzi F, Szydio RM, Craddock C, et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood. 2000;95:67-71.

145. Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: Prognostic relevance of the initial cell dose. Blood. 2002;100:397-405.

146. Olavarria E, Ottman OG, Deininger M, et al. Chronic Leukemia Working Party of the European Group of Bone and Marrow Transplantation (EBMT). Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2003;17:1707-12.

147. Olavarria E, Siddique Sh, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110:4614-7. doi: 10.1182/blood-2007-04-082990.

148. Tomblyn M, Lazarus HM. Donor lymphocyte infusion: the long and winding road: how should it be traveled? Bone Marrow Transplant. 2008;42:569-79. doi: 10.1038/bmt.2008.259. 

149. DeAngelo DJ, Hochberg EP, Alyes EP, et al. Extended follow-up of patients treated with imatinib mesylate (Gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation. Durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease. Clin Cancer Res. 2004;10:5065-71. doi: 10.1158/1078-0432.CCR-03-0580.

150. Duniop LC, Powles R, Singhal S, et al. Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant. 1996;17:365-9. pmid: 8704688.

151. Snyder DS, Nademanee AP, O’Donnell MR, et al. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999;13:2053-8. pmid: 10602428.

152. Laport GG, Alvarnas JC, Palmer JM, et al. Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractioned total body irradiation-etoposide regimen. Blood. 2008;112:903-9. doi: 10.1182/blood-2008-03-143115.

153. Hoelzer D, Gökbuget N, Ottmann OG. Targeted therapies in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Semin Hematol. 2002;39:32-7. pmid: 12447850.

154. Avivi I, Goldstone AH. Bone marrow transplant in Ph+ ALL patients. Bone Marrow Transplant. 2003;31:623-32. doi: 10.1038/sj.bmt.1703899.

155. Fielding AK, Goldstone AH. Allogeneic hematopoietic stem cell transplant in Philadelphia-positive acute lymphoblastic leukemia. Bone Marrow Transplant. 2008;41:447-53. doi: 10.1038/sj.bmt.1705904.

156. Bachanova V, Weisdorf D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant. 2008;41:455-64. doi: 10.1038/sj.bmt.1705889.

157. Lee S, Kim YJ, Chung NG, et al. The extent of minimal residual disease reduction after the first 4-week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2009;115:561-70. doi: 10.1002/cncr.24026.

158. Forman SJ, O’Donnell MR, Nademanee AP, et al. Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1987;70:587-8.

159. Barrett AJ, Horowitz MM, Ash RC, et al. Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1992;79:3067-70.

160. Arico M, Valsecchi MG, Camitta B, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med. 2000;342:998-1006.

161. Dombert H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia – results of the prospective multicenter LALA-94 trial. Blood. 2002;100:2357-66. doi: 10.1182/blood-2002-03-0704.

162. Esperou H, Boiron JM, Cayuela JM, et al. A potential graft-versus leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from the French Bone Marrow Transplantation Society. Bone Marrow Transplant. 2003;31:909-18. doi: 10.1038/sj.bmt.1703951.

163. Gupta V, Yi QL, Brandwei J, et al. The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison. Bone Marrow Transplant. 2004;33:397-404. doi: 10.1038/sj.bmt.1704368.

164. Goldstoune AH, Chopra R, Buck G, et al. The outcome of 267 Philadelphia positive adults in the International UKALLXII/ECOG E2993 study. Final analysis and the role of allogeneic transplant in those under 50 years [abstract]. Blood. 2003;102:80a.

165. Martin TG, Gajewski JL. Allogeneic stem cell transplantation for acute lymphocytic leukemia in adults: advances in the treatment of adult acute lymphocytic leukemia. Hematol Oncol Clin North Am. 2001;15:97-120.

166. Abou Mourad YR, Fernandez HF, Kharfan-Dabaja MA. Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Biol Blood Marrow Transplant. 2008;14:949-58.

167. Stein A, Forman SJ. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant. 2008;41:439-46. doi: 10.1038/bmt.2008.1.

168. Kovacsovics T, Maziarz R.T. Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of imatinib treatment on remission induction and allogeneic stem cell transplantation. Curr Oncol Rep. 2006;8:343-51. pmid: 16901395.

169. Carpenter PA, Snyder DS, Flowers ME. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007;109:2791-3. doi: 10.1182/blood-2006-04-019836.

170. Merante S, Colombo AA, Calatroni S, et al. Nilotinib restores long-term full-donor chimerism in Ph-positive acute lymphoblastic leukemia relapsed after allogeneic transplantation. Bone Marrow Transplant. 2009; Feb 9. [Epub ahead of print]. doi: 10.1038/bmt.2009.6.

171. Collins Jr RH, Goldstein S, Giralt S, et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 2000;26:769-74.

172. Kolb HJ, Schmid C, Barrett AJ, et al. Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 2004;103:767-76. doi: 10.1182/blood-2003-02-0342.

173. Choi SJ, Lee JH, Lee JH, et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy follower by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant. 2005;36:163-9.

174. Deiniger MW. Milestones and monitoring in patients with CML treated with imatinib. Hematology Am Soc Hematol Educ Program. 2008;419-26.

175. Goldman J. Monitoring minimal residual disease in BCR-ABL-positive chronic myeloid leukemia in the imatinib era. Curr Opin Hematol. 2005;12(1):33-9. pmid: 15604889.

176. Raanani P, Ben-Bassat I, Gan S, et al. Assessment of the response to imatinib in chronic myeloid leukemia patients: comparison between the FISH, multiplex and RT-PCR methods. Eur J Haematol. 2004;73:243-50. doi: 10.1111/j.1600-0609.2004.00287.x.

177. Schoch C, Schnittger S, Bursch S, et al. Comparison of chromosome banding analysis, interphase- and hyper metaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia. 2002;16:53-9.

178. Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR.  Methods Mol Med. 2006;125:69-92. pmid: 16502578.

179. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia. Blood Rev. 2006;20:29-41. doi: 10.1016/j.blre.2005.01.008.

180. Wang Y, Wu D, Sun A, et al. Allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in second chronic phase attained by imatinib after onset of blast crisis. Int J Hematol. 2008;87167-71. doi: 10.1007/s12185-008-0032-4.

181. Branford S, Cross NC, Hochhaus A, et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukemia. Leukemia. 2006;20:1925-30. doi: 10.1038/sj.leu.2404388.

182. Muller MC, Saglio G, Lin F, et al. An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007;92:970-3. doi: 10.3324/haematol.11172.

183. O’Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood. 2004;103:451-5. doi: 10.1182/blood-2003-02-0371.

184. Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood. 2004;104:2926-32. doi: 10.1182/blood-2004-03-1134.

185. Jabbour E, Kantarjian HM, Abruzzo LV, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2007;110:2991-5. doi: 10.1182/blood-2007-01-070045.

186. Martynkevich IS, Martynenko LS, Ivanova M.P, et al. Clonal evolution in Ph-positive CML Gleevec treated patients. Bulletin Hematol. 2007;3(1):30-4. Russian.

187. Machova Polakova K, Zmekova V, Rulcova J, et al. BCR-ABL mutations in chronic myeloid leukemia – Not only detection. Leukemia Lymphoma. 2008;49:1620-2.

188. Spinelli O, Peruta B, Tosi M, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. Haematologica. 2007;92:612-8. doi: 10.3324/haematol.10965.

189. Thörn I, Botling J, Hermansson M, et al. Monitoring minimal residual disease with flow cytometry, antigen-receptor gene rearrangements and fusion transcript quantification in Philadelphia-positive childhood acute lymphoblastic leukemia. Leuk Res. 2009;33:1047-1054. doi: 10.1016/j.leukres.2008.11.031.

190. Willis SG, Lange T, Demehri S, et al. High sensitivity detection of Bcr-ABL kinase domain mutations in imatinib-naïve patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood. 2005;106:2128-37. doi: 10.1182/blood-2005-03-1036.

191. Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood. 2008;112:4437-44. doi: 10.1182/blood-2008-06-162388.

192. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007;109:58-60. doi: 10.1182/blood-2006-03-011239.

193. Fava C, Kantarjian HM, Jabbour E, et al. Failure to achieve a complete hematologic response at the time of achievement of a major cytogenetic response with second generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood. 2009;00:00-00. doi: 10.1182/blood-2008-10-184960.

194. Jones LK, Saha V. Philadelphia positive acute lymphoblastic leukemia of childhood. Br J Haematol. 2005;130:489-500. doi: 10.1111/j.1365-2141.2005.05611.x.

195. Iacobucci I, Lonetti A, Cilloni D, et al. Identification of different Ikaros transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method. Haematologica. 2008;93:1814-21. doi: 10.3324/haematol.13260.

196. Iacobucci I, Lonetti A, Messa F, et al. Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance. Blood. 2008;112:3847-55. doi: 10.1182/blood-2007-09-112631.

197. Mullighan CG, Miller CB, Phillips LA, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453:110-4. doi: 10.1038/nature06866.

198. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360:470-80.

199. Georgopoulos K. Acute lymphoblastic leukemia – on the wings of IKAROS. N Engl J Med. 2009;360:524-6.

200. Rieder H, Ludwig WD, Gassmann W, et al. Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Br J Haematol. 1996;95:678-91. pmid: 8982045.

201. Thomas X, Thiebaut A, Olteanu N, et al. Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther. 1998;40:119-28. pmid: 9698220.

202. Wetzler M, Dodge RK, Mrozek K, et al. Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia: a study of the Cancer and Leukemia Group B. Br J Haematol. 2004;124:275-88.

203. Moormann AV, Harrison CJ, Buck GA, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALL111/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109:3189-97. doi: 10.1182/blood-2006-10-051912.

204. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008;111:2563-72. doi: 10.1182/blood-2007-10-116186.

205. Li Y, Qiu L, Zou D, Zhao Y, et al. Additional chromosomal abnormalities and their prognostic significance in adult Philadelphia-positive acute lymphoblastic leukemia: with or without imatinib in chemotherapy. Ann Hematol. 2009; Mar 10. [Epub ahead of print]. doi: 10.1007/s00277-009-0720-z.

206. Yanada M, Takeuchi J, Sugiura I, et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica. 2008;93:287-290. doi: 10.3324/haematol.11891.

207. Paulsson K, Cazier J-B, MacDougall F, et al. Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease. Proc National Acad Sci. 2008;105:6708-13.

208. Eiring AM, Neviani P, Santhanam R, et al. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood. 2008;111:816-28. doi: 10.1182/blood-2007-05-090472.

209. Laport GG, Alvarnas JC, Palmer JM, et al. Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation-etoposide regimen. Blood. 2008;112:903-9. doi: 10.1182/blood-2008-03-143115.

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Introduction

The Philadelphia (Ph1)-chromosome was discovered in 1960 year [1] and for a long time it was considered to be a specific marker of chronic myeloid leukemia (CML). Later it was found that Ph1 is the result of reciprocal translocation between chromosomes, i.e. t(9;22)(q34;q11) [2]. In fact, this translocation results in the formation of two hybrid genes, BCR-ABL on the Ph1 chromosome and ABL-BCR on 9q+. The chimeric BCR-ABL fusion product is a tyrosine kinase. Its activity accounts for more than 95% of CML cases [3-5], and 10–20% of adults and about 2–5% of children with B-cell acute lymphoblastic leukemia (ALL) [6, 7]. Occasional bona fide Ph1-positive (Ph+) cases among acute myeloid leukemias (AML) [8, 9], lymphomas [10], multiple myeloma [11], myelodysplastic syndromes [12, 13], ‘essential thrombocythemia’ [14-16], and chronic neutrophilic leukemia (CNL) [17] have also been published.

The treatment of CML has been recently revolutionized by the development of imatinib mesylate (IMT, Gleevec, STI571) and other tyrosine kinase inhibitors (TKIs), which report to be targeted inhibitors of BCR-ABL [18-20].

I. Laboratory Tests

1.1. t(9;22)(q34;q11) translocation detection
Translocation (9;22) in newly diagnosed leukemia patients is detected using conventional cytogenetics (CC) supplemented by chromosome banding analysis (Fig. 1), and supported by reverse transcriptase polymerase chain reaction (RT-PCR) [21]. The chromosome banding analysis remains the best first-line genetic test for assessing any new acute leukemia because it screens for t(9;22) as well as for alternate and nonrandom additional genetic defects, including +der(22)t(9;22), 9p abnormalities, i(17q), -7, +8, +19, +21, and so on [21].

2009-4-en-Mamaev-Figure-1.JPG

Figure 1. Karyotype of bone marrow cell from a female patient with Ph-positive acute lymphoblastic leukemia, relapsed after allogeneic stem cell transplantation, made in Germany. It illustrates two Ph-chromosomes with typical translocation t(9;22)(q34;q11) and multiple additional numeral and structural chromosome changes. 2n=52, XX, +X, t(9;22)(q34;q11), +der(22)t(9;22), +del(4)(q27), -8, +i(8)(q10), +10, +14, -20, +der(20q+), +21.

1.2. Fluorescence in situ hybridization
One of the sensitive approaches for diagnosis of Ph+ leukemias is fluorescence in situ hybridization (FISH). The FISH technique can be applied directly to non-dividing cells, it detects both cryptic and complex BCR-ABL rearrangements, including three-way translocations as well as some breaks outside of the usual major and minor cluster regions (Fig. 2). Sensitivity of the method is about 1 cell in 200 tested, or 0.5%. A problem with around 1% of CML patients who have a Ph1-negative karyotype because of a cryptic BCR/ABL1 fusion is that it can only be located by FISH at chromosome 22q11, 9q34 or a third chromosome [22-24].

2009-4-en-Mamaev-Figure-2.JPG

Figure 2. Karyotype (A) and fluorescent in situ hybridization (FISH) analysis findings on chromosomes (B, D) and interphase nuclei (C) from a patient with chronic myeloid leukemia, illustrating atypical translocation of t(6;22)(q21;q11), which was associated with formation of fusion ABL/BCR gene on chromosome der(22)t(6;22). 2n=46, XY, t(6;22)(q21;q11). The fusion gene (yellow color) (B, C) was evidenced by means of fluorescent probes to ABL (red) and BCR (green) genes. On the other hand, the atypical translocation t(6;22) was evidenced  (D) by means of fluorescent probe WCW22 directed to chromosome number 22. After FISH each chromosome plate contains three brightly stained signals, including those on der(22)t(6;22) (small signal), unchanged chromosome 22 (right big signal) and der(6)t(6;22) (left big signal). Magnification x900.

1.3. Southern blot analysis
Southern blot analysis reliably identifies BCR gene rearrangement using probes targeting either the M-bcr or m-bcr breakpoint. Although this technique is quite helpful in confirming the BCR defect associated with CML or ALL, the Southern blot method is time-consuming and costly [22].

1.4. Amplification technologies
RT-PCR is the most sensitive of today's methods for detecting BCR-ABL. One of the advantages of RT-PCR is an ability to differentiate p210 from p190 forms of BCR-ABL [22]. It should be mentioned here that the recently developed real-time quantitative PCR (RQ-PCR) technique allows the assessment of trends in the BCR-ABL load over time and, hence, the chance to control minimal residual disease (MRD) [25]. 

1.5. Analysis of BCR-ABL kinase domain (KD) mutations
There are several molecular techniques that can detect BCR-ABL kinase domain (KD) mutations in Ph+ leukemias that are resistant to tyrosine kinase inhibitors (TKI). A more effective technique among them is a recently modified liquid chromatography (D-HPLC) [26-33].  

1.6. Gene expression profiles and micro array analysis
A major advantage of array technology is the ability to evaluate an expression of thousands of genes simultaneously. For this purpose RNA is extracted from the patient’s sample and converted to labeled cRNA or cDNA before being applied to an array of complementary probes that allows the successful differentiation of BCR-ABL cases from other forms of ALL [34].

II. Laboratory and clinical findings in Ph-positive disorders

2.1. Structure of the BCR-ABL fusion genes and their transcripts
The breakpoint in the ABL gene occurs within a >300-kb segment at the 5’end of the gene, either upstream of the first alternative exon Ib, between exons Ib and Ia, or downstream of axon Ia. In the vast majority of CML patients and in about one third of ALLs, the breakpoint in the BCR gene is revealed within a 5.8-kb region known as the major breakpoint cluster region (M-bcr), spanning 5 exons historically named b1 to b5, now known to be exons e12 to e16 of the BCR gene. Regardless of the position of the ABL breakpoint, processing of the primary BCR-ABL transcript usually results in hybrid BCR-ABL mRNA molecules with e14a2 and or e13a2 junction encoding a p210BCR-ABL fusion protein [7]. In two thirds of ALLs and in very rare cases of CML and AML patients, the breakpoint in BCR falls further upstream, in the long (54.4 kb) intron between the two alternative exons e2’ and e2, known as the minor bcr (m-bcr). In these circumstances, exons e1’ and e2’ are removed by splicing, and the hybrid BCR-ABL transcript contains an e1a2 junction, and is translated into a smaller 190-kD BCR-ABL fusion protein named p190BCR-ABL. Thus, e14a2 (b3a2) and/or e13a2 (b2a2) fusion transcripts and p210BCR-ABL protein[s] are more characteristic for CML. In contrast, the p190BCR-ABL protein arising from the minor BCR rearrangement producing the e1a2 and/or e1a3 fusion transcript is seen in the majority of cases of Ph+ ALL. Meantime, the expression of e13a2 and/or e14/a2 fusion transcripts is noted in ALL, especially in adult patients [35, 36]. Furthermore, in Ph+ ALL patients some atypical BCR-ABL transcripts, including e1a3, e13a3, and e6a2, have recently been detected [36]. Additionally, occasionally cases of CML with e1a2, e19a1 and e19a2 transcripts [33, 37, 38] have been reported; the clinical significance of which remains unclear.

2.2. Prevalence of BCR-ABL


2.2.1. CML
The vast majority of CML patients have a p210 breakpoint of ABL-BCR gene, and they retain this genotype when their disease progresses to blast crisis (BC). There is also a possibility for coexistent p190 and p210 transcripts in 8% patients with accelerated-phase or BC CML [39].  

It is important to clarify whether the position of the breakpoint within the M-bcr region (5’ M-bcr v 3’ M-bcr), or the type of fusion transcript (for instance, e13a2 v e14a2) somehow influences the disease phenotype or not. The debate has been going on for several years, with some evidence in favor [33, 40, 41] and some against [42, 43] a possible link between M-bcr breakpoint location and disease features, that remains to be cleared up.

Currently many atypical BCR-ABL transcripts are documented in patients with CML, including e1a3, e6a2, e8a2, e13a3, e14a3, e19a2 and others [7, 36, 44]. The most frequent transcripts among them are e6a2 and e1a3 [36]. The clinical course of Ph+ CML with BCR breakpoints outside the above three main cluster regions (e.g. with e1a3) was more benign [45-48], although myeloid BC CML developed in most of them [36, 38, 47, 49]. It has been actively discussed that the poor prognosis of leukemias in the patients with atypical ABL/BCR transcripts might be associated with their lacking the (GET)/Abl-like domain of BCR [50]. This conclusion was based on the findings of a case in Ph-negative CML, where BCR-ABL fusion was recognized by FISH staining of metaphase chromosomes only [51], and wherein e6a2 atypical ABL-BCR fusion, encoding a hybrid p195BCR-ABL protein [50] was detected.

2.2.2. ALL

The BCR-ABL fusion gene is found in around 25% of adult ALL cases [36, 52-54] and in 2% of children [55-56]. Minor breakpoint transcripts (e1a2) encoding for p190 protein, are found in 59% to 70% of positive cases, whereas major breakpoint transcripts (e13a2 or e14a2) encoding for p210 protein are detected in 23% to 30% of cases [57]. Thus, the typical BCR-ABL mRNA transcripts are e1a2, e13a2, and e14a2. At the same time 3% to 19% of ALL patients can express both p210 and p190 fusion transcripts [35, 52-54, 57]. Preliminary data show a high prevalence of p210 copies with respect to copies of the p190 transcript in p190/p210+ cases [35]. Finally, atypical BCR-ABL transcript products are revealed in 1–2% of all Ph+ ALL cases, and include such atypical transcripts as e1a3 (most often), e6a2, e13a3, and e19a2 [7, 36, 58, 59].

The presence of BCR-ABL in ALL is interesting for two reasons. First, the patients with Ph+ ALL have a poor prognosis under conventional therapy [52] and are, therefore, considered high-risk patients and primary candidates for both intensified therapy regimens and alloSCT [36]. Secondly, BCR-ABL positive patients can have a significantly better prognosis under treatment regimens with ABL TKIs such as imatinib [60], dasatinib [61, 62], nilotinib [63] etc., and should take them whenever possible.

2.2.3. Clinical  significance of BCR/ABL isoforms
The majority of BCR-ABL positive adult [52] and childhood ALLs [55, 56, 64] have common or pre-B cell immunological variants with frequent co-expression of CD10, CD13, and CD33 antigens. A special analysis of gene expression patterns showed PILRB, STS-1 and SPRY genes to be overexpressed, whereas TSPAN16 and ADAMTSL4 genes are under-expressed in p190BCR-ABL-positive cases relative to p210BCR-ABL-positive ALLs [54, 57]. No difference was seen in the overall survival of patients with p190BCR-ABL-positive vs p210BCR-ABL-positive ALL. On the basis of this data a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1) has been constructed which, in turn, correlated with overall survival (p=0.0001) in BCR-ABL-positive adult ALL, independent of age (p=0.25) and WBC count at presentation (p=0.003) [54].

The overall response to induction therapy (without TKIs) as well as the type of transplants did not differ significantly between patients with p190+ and p210+ transcripts, although the probabilities of DFS and OS are dependant on BCR/ABL isoforms [35]. Multivariate analysis performed in BCR/ABL+ patients showed that among the variables analyzed (i.e., age, white cell count, expression of CD34, CD10, CD13 and CD33, and type of BCR/ABL transcript), the presence of the p190 fusion transcript was the only powerful independent prognostic factor that favorably influenced disease-free survival (p=0.031) [35]. Besides this, the p190 fusion appears to be the only independent prognostic factor with regard to DFS and OS [35, 65].

2.3. Treatment of BCR-ABL+ leukemias with TKIs

2.3.1. CML
The deregulated tyrosine kinase activity of the BCR-ABL and represents an extremely attractive target for therapeutic intervention. The first original Abl tyrosine kinase inhibitor (TKI) imatinib mesylate (imatinib, IMT) has been developed for clinical use as a result of collaboration between Brian Druker [66-69] and investigators at Ciba-Geigy [70]. Its efficacy was evidenced both on cell lines and the great material collected from patients with CML [69, 71-83]. With a median follow-up of 19 months [77], the estimated rates of complete hematologic remission (CHR) for patients whose initial treatment was imatinib were 96%; major cytogenetic response (MCyR) was 87%; and from CCyR-treated patients, 76%. In patients with accelerated phase CML, imatinib results in a CHR rate of 82% and a MCyR rate of 24% [84]. However, in BC patients CML responses to IMT were of short duration [68, 71], although around 7% patients remain alive after a median observation time of 6 years [85]. In this case imatinib results in a CHR rate of 8–11%, having a MCyR response rate of 16% only, and the median time to relapse in responding patients with BC was about 3 months [86].

The striking efficacy of IMT in CML [25, 72, 74, 75, 78, 79, 87-89] has established this therapy as a new standard for care for the disease. However, resistance is an emerging problem. which has prompted the design of several second-generation TKIs. To overcome the resistance to imatinib [90-93], high-dose IMT therapy was used [94] as well as alternative second-generation TKIs, including dasatinib, nilotinib, INNO-406, MK-0457, and bosutinib (BST).

Dasatinib (BMS-354825; Bristol-Myers Squibb) [68, 92] is active against many of the kinase domain mutants responsible for imatinib resistance [95, 96]. One remarkable exception appears to be the T315I mutation. As shown in a special study of 21 Ph+ patients who failed to respond or relapsed during dasatinib therapy, all patients but one had mutations at residue 315 and/or at residue 317 [30].

Clinical experience in treatment of IMT-resistant or refractory CML patients with dasatinib and nilotinib has been recently reviewed by Goldman [75]. As a result, MHR rates with dasatinib among intolerant or resistant to imatinib patients were 63% for accelerated phase CML (follow-up > or =9 months), 34% for patients with myeloid BC CML, and 35% for those with lymphoid BC CML (follow-up > or =12 months; START-B and START-L trials) [92]. In another study, CHR responses with dasatinib were achieved in 81% IMT-resistant patients with CP CML, while MCyR was demonstrated in 57% of patients [97]. As for high resistance to dasatinib, it was related to the T315I and F317L Abl KD mutations [30, 98, 99].

The next of the second-line BCR-ABL TKI is nilotinib (formerly AMN107), which is 20 to 50 times more active than imatinib against CML cells [87, 93]. The first experience with nilotinib in 119 IMT-resistant patients with CML showed the following. Of 30 patients at BP of the disease, 13 (39%) experienced HR and 9 patients (27%) had a CyR, of whom 6 had a MCyR (Ph+ cells in metaphase, ≤35%). Of 46 patients with accelerated phase CML 33 had a HR and 22 had a CyR. Lastly, 11 of 12 patients with the CP CML had a CHR [90]. As for the resistance to nilotinib, it was again associated with T315I and F317L ABL KD mutation [30] that allows a choice of such TKIs as INNO-406 or MK-0457 for treatment patients with the above unfavorable mutations [30, 75, 98, 99].

2.3.2. ALL

The treatment of Ph+ ALL has also changed dramatically since imatinib was introduced [100-105]. Early phase I and II studies of imatinib in Ph+ ALL revealed its significant, albeit unsustain, activity against relapsed or refractory leukemias [73, 81, 106]. On the other hand, combined with chemotherapy, or even as a single agent, it can produce CR rates of 90% or higher in newly diagnosed patients [6, 85, 100-102, 104, 105, 107-109]. However, these responses were not durable (median, 9 months) [60], whereas further intensification of chemotherapy has had no substantial impact on the unfavorable course of de novo Ph+ adult ALL or in patients who fail first-line therapy [110, 111]. A special study of alternating vs concurrent schedules of imatinib and chemotherapy as front-line for Ph+ ALL demonstrated that co-administration of imatinib and induction cycle 2 results in a CHR rate of 95% and RT-PCR negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (p=0.01). Further, in each cohort, 77% of patients underwent alloHSCT in CR1. As a result, both schedules of imatinib had acceptable levels of toxicity to patients, but concurrent administration of IMT and chemotherapy had resulted greater anti-leukemic efficacy [109].

It should be noted also, that the Ph+ ALL is very characteristic for elderly patients, wherein it has a poor prognosis, with a low CHR rate, high induction mortality, and short remission duration [112]. On the other hand, imatinib as a single agent for elderly patients is toxic enough whereas a potentially curative alloHSCT is not generally applicable [110]. Therefore, it is noteworthy, that the overall CHR rate in the group of elderly patients where imatinib was used for remission induction, was significantly higher (93.5%) than that in patients wherein for induction remission was used multi-agent chemotherapy (50%, p=0.0001) [112].

Despite the similar cytogenetic and molecular characteristics, the resistance to imatinib in patients with Ph+ ALL develops earlier and more frequently than that in CML, and therefore second-line TKIs are necessary. In part, CHR and CyR may be achieved with dasatinib [68, 90], and nilotinib [113], which appear to be ineffective in cases with T315I and F317L KD mutations [99].

Analogous with CML, the best drugs for treatment of patients who seem to be resistant to or intolerant to imatinib, were dasatinib, nilotinib, or bosutinib [6, 63, 91]. According to published data [90, 92], dasatinib induced CHRs in 42% of patients with IMT-resistant Ph+ ALL (follow-up > or =12 months), which is even higher than those in patients with myeloid and lymphoid variants of BC CML.

2.4. BCR-ABL kinase domain (KD) mutations

2.4.1. CML
More than 90 different point mutations encoding for distinct single amino acid substitutions in the BCR-ABL KD have been so far identified, but 10 of them occur in >80% of the cases [20]. The presence of KD mutations has been studied mainly in the advanced phase, and in CP patients when they become resistant to imatinib [113]. Meantime, a special screening for the mutation status of 319 newly-diagnosed patients with CP CML showed the identification of a mutation without other evidence of imatinib resistance to be highly predictive for loss of CCyR (RR, 3.8; p=0.005) and for progression to advanced phase (RR, 2.3; p=0.01). On the basis of this data it was concluded that mutations in the P-loop (excluding residue 244) were associated with a higher risk of progression than mutations elsewhere [114]. Although T315I was the most frequent mutant to emerge, other mutations like T315A, V299L, and F317I were detected that demonstrated retention of sensitivity to imatinib and potentially to nilotinib [30, 115]. Among patients with CP CML who develop (secondary) resistance to imatinib, 30% to 50% have one or more BCR-ABL KD mutations [116-120]. Some DK mutations (V299L, T315I, and F317L/I) were greatly specific for dasatinib [122-125], and others (G250E, Y253H, E255K, T351I, or F311I) for NLT [122] or MK-0457 [126]. Serial investigations showed that the longest period between detection of a mutation and subsequent relapse is observed in patients harboring M351T mutations [125]. In contrast, patients harboring T315I or P-loop mutations demonstrated a 5–25-fold need for immediate withdrawal of imatinib [28, 29].

According to the three largest retrospective studies [28, 117, 127], the incidence of the T315I mutation in IMT-resistant patients was 4%, 11%, and 19%, respectively whereas the frequency of P-loop mutations in the same series of patients was much higher, being 28%, 46%, and 39%, respectively. In general, survival of patients with this mutation remains dependent on the stage of the disease, it having an indolent course in many CP patients [98]. Meantime it is expected that patients with the T315I mutation will also reveal resistance to the treatment with either dasatinib or nilotinib [29, 30, 68, 87, 128]. That is why INNO and ON012380, which are binding regions of BCR-ABL other than the ATP binding pocket, are recommended first of all for these patients [30]. It should be noticed that except for the lack of response to second TKIs (p=0.002), other patient characteristics, including outcomes between patients with T315I and those with other or no mutations were similar.

So the prognostic significance of such KD mutations as T315I, and P-loop region of ABL is undoubted. It is also important that T315I and P-loop mutations were preferentially presented in accelerated phase and of BC CML, compared to other types of mutations in CP CML (p=0.003). In addition, overall survival (OS) after imatiunib initiation was significantly worse for P-loop (28.3 months) and for T315I (12.6 months), than that for other mutations (p=0.0004). Meantime, multivariate analysis of data from CP patients demonstrated a worse OS for P-loop mutations only (p=0.014), but a worse progression-free survival (PFS) for T315I mutations (p=0.014).

The vast number of mutation reports published later have demonstrated number of IMT-resistant patients with different amino acid substitution to be greatly high [89]. Many of these BCR-ABL DK mutations are associated with a relatively modest increase in resistance to imatinib, which may be overcome by dose increase only [30, 51]. On the contrary, mutations such as T315I, and those falling within the P-loop region, i.e., G250E, Y253F/H, and Ee55K/V, confer a highly resistant phenotype [28-30]. An analysis of BCR-ABL mutations by means of denaturating high-performance liquid chromatography found them in 127 of 297 (43%) of the available Ph+ patients. These mutations were revealed in 27% of CP CML patients (14% treated with IMT frontline; 31% treated with IMT post INF-α failure), 52% of accelerated-phase patients, 75% of myeloid BC patients, and 83% of lymphoid BC/Ph+ ALL patients. It should be mentioned that mutations were associated in 30% of patients with primary resistance to imatinib (44% hematologic and 28% cytogenetic), and in 57% of patients with acquired resistance (23% patients who lost CyR; 55% patients who lost HR; and 87% patients who progressed to accelerated phase/BC). On the basis of these findings the following conclusions were drawn. Firstly, amino acid substitution of seven residues (M244V, G250E, V253F/H, E255K/V, T315I, M351T, and F359V) accounts for 85% of all resistance-associated mutations. Secondly, the search for mutations is important both in case of IMT failure and in case of a loss of response at the hematologic or cytogenetic level.

It is interesting to note that in the majority of the resistance patients with CML, mutations were detectable at various intervals prior to hematologic relapse (range 0.9–44.2 months), which was registered at a median of 12.9 months after the start of imatinib therapy. On the other hand, BCR-ABL mutations first became detectable at a median of 5.8 months (range 0–30.5) after commencing imatinib. The difference between time to hematologic relapse and earliest detection of a mutation was highly significant (p<0.0001).

Since BCR-ABL KD mutations in some of CML and Ph+ ALL patients can be found without clinical evidence of resistant disease [26, 129-131], the questions arises as to when tests for DK mutations should be done and by what methods. According to international recommendations, BCR-ABL KD mutation screening in chronic phase CML is only recommended for patients with inadequate initial response to TKIs or those with evidence of loss of response. Mutation screening is also recommended at the time of progression to accelerated or BC CML [26, 132, 133]. Criteria for inadequate initial response (i.e., primary resistance) include lack of CHR, mCyR (66-95% Ph+ metaphases in BM) or lack of MCyR at 3, 6, and 12 months respectively which are similar to the criteria adopted by the European Leukemia Net [89]. Criteria for loss of response to TKI (i.e., secondary resistance) are also based on cytogenetic and/or hematological relapse, with variable use of molecular relapse criteria. One proposed molecular trigger for mutation testing is a tenfold or greater increase in BCR-ABL transcript levels, although smaller rises in BCR-ABL transcript levels may also be predictive of mutation development.

2.4.2. ALL
In comparison with CML, BCR-ABL KD mutations in relapsed Ph+ ALL occur much more frequently (80% to 90% of cases), especially in patients who have been treated with TKIs as initial or ongoing therapy [26, 32, 33, 134].  However, more sensitive detection methods reveal low levels of a point mutation clone in some Ph+ ALL cases before exposure to TKIs. The latter convinces that resistant clones in Ph+ ALL may precede TKI selection [134].

A study of the ABL KD mutation status in newly diagnosed Ph+ ALL patients showed that IMT-resistant TK domain mutations were detected in 38% patients even before exposure to IMT. Although the frequency of the mutant allele was low in such patients at the time of relapse, the same mutation was present as the dominant clone in 90% of the relapsing cases [134].

2.5. Hematopoietic stem cell transplantation (HSCT)

2.5.1. CML
Until the advent of imatinib, alloHSCT was considered to be the only known curative therapy for patients younger than 50 years having suitable HLA-identical siblings, HLA-matched family members, or HLA-matched volunteer unrelated donors [75]. Although the morbidity and indeed mortality attributable to the procedure were both appreciable, the probability of survival could be predicted with reasonable accuracy via the scoring system developed for the European Group for Blood and Marrow Transplantation (EBMT) [135]. Graft-versus-leukemia (GvL) effects contribute substantially to the curative potential of this approach [25, 136]. However, relapse occurs in approximately 5% to 20% of patients transplanted in chronic phase. While some patients remain in a stable MRD status, others rapidly progress to overt clinical relapse [137]. In order to re-induce MolR through augmenting or re-establishing the GvL effect, cessation of immunosuppression [138] and, particularly, donor lymphocyte infusion (DLI) are standard approaches for patients with relapse after alloHSCT [139, 140]. Unfortunately, this approach is frequently associated with substantial risk, mainly induction of graft-versus-host disease (GvHD) or BM suppression [139-144], which in large surveys have been observed in approximately 48% and 18% of patients [25, 145]. As a result, over 80% of patients with low risk of GvHD (i.e., 0–2) had a probability of being alive at 5 years [146] and the probability of subsequent relapse for patients free of detectable CML was extremely low [147].

Although the treatment with imatinib is less toxic, it may not cure the disease and, being used for a long time makes it very expensive. Additionally, resistance to imatinib can also occur in the course of the therapy. Therefore, alloHSCT for the treatment of some CML patients remains  necessary [25]. Firstly, transplanted HSC have anti-leukemic activity and contribute to maintaining remissions. Secondly, the effect of imatinib may be increased by potential side effects of DLI and vice versa [148]. Since suppression of MRD with imatinib can theoretically allow re-establishment of complete chimerism as well as restore full GvL effects, this approach has been recently tested successfully in clinical practice [37, 77, 149]. Additionally, a special molecular investigation showed that 70% of patients with CML who relapsed after alloHSCT can achieve CMolR after imatinib treatment and DLI [139, 140, 142, 148].

2.5.2.  ALL
The poor outcome with conventional chemotherapy made alloHSCT an attractive option for patients with Ph+ ALL [100, 101, 108, 109, 150-157]. The first study of allo BMT in 10 patients with Ph+ showed that 4 patients died of transplant-related complications, while 6 patients survived the transplant and remained in CR (median follow-up; 19 months) [158]. A retrospective analysis in 67 Ph+ ALL patients aged 5–49 years who underwent alloHSCT, showed that 21 of them (31%) were in continuous CR≥2 years after transplant [159]. There were no significant differences in TRM, DFS, and relapse rate between patients who had been transplanted in first or later CR. However, 2-year DFS was much lower in patients who had never achieved CR before transplant. Better results were reported later [151, 154, 160, 161]. For instance, Snyder et al [151] reported a 65% DFS rate (15/23) at 3 year post-transplant, whereas the estimated relapse rate during that period was only 12%. According to data from the French Bone Marrow Transplantation Society [162], in a study where 76 adult patients were in CR1 at the time of transplant, 2-year OS was demonstrated in 50% of patients, whereas the 2-year relapse incidence rate was 37%. In the largest prospective alloHSCT study (conducted during the pre IMT era), 5-year OS was superior in those who underwent MRD alloHSCT compared with chemotherapy or autologous HSCT [163, 164]. Unfortunately, despite its efficacy, currently only 20% to 60% of patients actually undergo alloHSCT. Moreover, even after alloHSCT in CR1 the probability of relapse for Ph+ ALL patients is approximately 30%, which together with a high transplant-related mortality of 20% to 40% highlights the limitations of current therapy [109, 165, 166].

The recent appearance of TKIs in clinical practice has changed the up-front treatment paradigm and appears to affect the outcome after HCST [167]. In contrast with CML, wherein TKIs have changed our attitude to HSCT as the treatment of first choice [168], TKIs in Ph+ ALL appear to be seen only as a “bridge to transplant”, helping more patients to achieve and maintain sufficiently durable remission before [156] or after [63] HSCT. The latter is desirable to undergo in CR1. In such a case the long-term survival rates may be greater than 35%. Furthermore, the results can be essentially improved after first-line imatinib interim treatment [107, 157]. The data suggests that the 3-year estimated probabilities of relapse, DFS, and OS were 3.5% vs 47.3% in controls (p=0.02), and 78.1% vs 38% in controls (p=0.001), respectively, without much difference in the transplant-related toxicities. In this context, other studies have also demonstrated the feasibility of giving imatinib following alloHSCT for BCR-ABL+ ALL either preemptively or to treat any MRD detected after transplant prior to relapse instead of using a donor lymphocyte infusion [169, 170]. The management of patients with Ph+ ALL relapsing after alloHSCT represents a major challenge with limited chances of success. The efficacy of DLI in Ph+ ALL is much lower that that in CML [171], which is explained by the diverse immune escape mechanisms of ALL blasts from GVL effects of DLI [172]. On the other hand, the addition of cytoreductive chemotherapy to DLI does not seem to improve the outcome of relapsed ALL patients [173], whereas  a combination of TKIs and DLI may be greatly effective [63].

2.6. Monitoring treatment and/or minimal residual disease

2.6.1. CML

2.6.1.1. Blood counts and bone marrow karyotyping

Complete blood counts should be performed at least weekly until they have stabilized, with greater intervals thereafter. Once CHR has been documented, monitoring continues with karyotyping of bone marrow metaphases, which is recommended at 6, 12, and 18 months, or until CCyR has been achieved [38, 89, 174, 175]. If there are fewer than 20 metaphases, the cytogenetic response can be validated by determining the level of BCR-ABL transcripts and by molecular cytogenetics, or FISH. Of note is that FISH can be performed on metaphases or more frequently and more conveniently on interphase cells (IP-FISH) [38, 176]. In fact, all FISH data correlates very significantly with chromosome banding data [177], as well as with BCR-ABL transcript levels [176, 177]. Moreover, FISH can detect deletions of the long arm of chromosome 9 and variant translocations.

2.6.1.2.  Monitoring BCR-ABL transcript levels
Molecular monitoring of BCR-ABL transcript levels with RQ-PCR has become an integral part of management of patients with CML [132, 178-180]. This is particularly relevant in the era of imatinib therapy, when residual levels of leukemia usually fall below the level of detection via bone marrow cytogenetic analysis. Indeed, even small increases in the BCR-ABL level can identify patients with TK domain mutations that lead to IMT resistance.

Currently, the best molecular approach for monitoring BCR-ABL transcript levels is considered to be RQ-PCR [133, 178, 179]. The best gene for internal reference appears to be β-glucuronidase and not the widely-used ABL gene [180]. In fact, a failure to achieve a major MolR by 18 months after starting imatinib therapy is considered a suboptimal response requiring careful re-evaluation and possible reassessment of therapy [92]. Various prerequisites for achieving optimal sensitivity and standardization have been agreed upon and published [133, 181, 182]. According to recent international reporting scale, major MolR is established at BCR-ABL 0.1%, whereas a value of 1.0% is approximately equivalent to the achievement of CCyR  [38].  From a practical point of view, it has been suggested that RQ-PCR must be performed every 3 months even in patients who achieve a MolR [179]. If, after alloHSCT, the attainment of BCR-ABL-negative status is conferred, the overall survival is significantly improved (57% vs 12%; p=0.006) [176]. In contrast, in the case where BCR-ABL levels increase, there is the possibility of identifying the patients who do not respond properly to the proposed therapy or even to start the search for BCR-ABL mutations [183, 184]. However, even considering that RQ-PCR is fundamental for monitoring patients with CCyR, there are other reasons to suggest that cytogenetics should not be completely replaced by RQ-PCR in the follow-up of CML patients. Firstly, additional chromosome abnormalities present at diagnosis or arising during the disease may have a prognostic influence [183]. Secondly, there is evidence of clonal cytogenetic abnormalities in the Ph-negative cells [185, 186] which appeared after suppression of Ph-positive clone by imatinib and, in a majority of cases, could be a characteristic of future myelodysplasias [38]

2.6.1.3. Monitoring BCR-ABL kinase domain mutations
A mutation at the TK domain of the oncogenic BCR-ABL protein is frequently detected in patients with CML who fail to respond to TKIs or lose the response [187>]. The best approach for screening for BCR-ABL mutations during therapy with TKIs is D-HPLC [28, 31]. The studies show that mutations may be detectable several months before relapse, but the occurrence of BCR-ABL mutations during imatinib therapy is predictive of relapse.
     
2.6.2. ALL

2.6.2.1. Cytogenetic monitoring

In contrast to CML, cytogenetic changes in Ph+ ALL in the course of chemotherapy do not last long. Therefore, the main tasks of cytogenetics, including FISH, in these patients are: a) to verify a CCyR; or, in turn, b) to detect a resistance to chemotherapy, TKI or HSCT.

2.6.2.2. BCR-ABL transcript level monitoring
BCR-ABL RNA transcripts are suitable molecular markers for MRD analysis and for guiding therapy [25, 188, 189]. However, MRD analysis with RT-PCR is affected by intra- and inter-assay variability, which appear to reflect different proportions of leukemic blast cells. A special investigation of samples from 56 patients showed levels of BCR-ABL to be higher in bone marrow than in peripheral blood. In fact, they did not differ when normalized to 100% blasts. Moreover, the numbers of BCR-ABL transcripts per blast in 25 sequential BM and 8 sequential PB did not change significantly during evolution of Ph+ ALL. As for the mean number of p210 copies per blast concern they were 1.1 log higher than that for p190 (p=0.0006).

2.6.2.3. BCR-ABL kinase domain mutation monitoring
In contrast to CML, pre-existence of mutations including the T315I mutation did not adversely effect either the CR rate following imatinib or chemotherapy induction or the achievement of BCR-ABL negativity in response to combination therapy, when compared with patients exhibiting only non-mutated BCR-ABL at diagnosis [190]. In our opinion, this might be explained by the earlier use of high-doses chemotherapy followed by alloHSCT.

2.7. Prognosis

2.7.1. CML
In the TKI era the prognosis for CML patients has greatly improved. The majority of patients can now expect to survive 10 to 20 years [74, 88, 191]. It is even possible that some patients treated for a number of years can stop the imatinib and be regarded as cured of their leukemia [192]. Hence, any possibility of recognizing the minority of patients who respond poorly to imatinib at the earliest opportunity is very important [193]. Therefore, a series of empirical recommendations developed on behalf of the European LeukemiaNet (Table 1) [89] are used by clinicians to identify those CP CML patients responding poorly to imatinib at standard dosage. As for the other prognostically poor and verified factors in CML patients, they include the following: a) age; b) advanced stages CML; and c) BCR-ABL domain mutations, mainly, T315I.

Table 1. Modified European LeukemiaNet definition of failure and suboptimal response for previously untreated, early CP CML patients treated with 400 mg IMT daily
Failure implies that the patient should be moved to other treatments whenever available; NA indicates not applicable; HR, hematological response; CHR, complete HR; CyR, cytogenetic response; CCyR, complete CyR; MMolR, major molecular response; ACA, additional chromosome aberrations, and TK tyrosine kinase

Time Failure Suboptimal response Warnings
Diagnosis NA NA High risk
      del 9q+; addit chrom abnormalities (ACA) in Ph+ cells
3 months No HR Less than CHR  
6 months Less than CHR Less than partial CyR (Ph+ >35%)  
12 months Less than partial CyR (Ph+ >35%) Less than CCyR Less than MMolR
18 months Less than CCyR Less than MMolR  
At any time Loss of CHR; loss of CCyR; TK domain mutation ACA in Ph+ cells; Loss of MMolR; TK domain mutation Any rise in transcript level; ACA in Ph- cells

2.7.2. ALL
The prognosis of Ph+ ALL – whatever the fusion protein – is poor in both adults and children [70, 194]. Detailed analysis of prognostic-related factors showed that deletion of the IKZF1 gene [195-199], as well as the secondary chromosome aberrations at diagnosis [200-204], in addition to t(9;22), had a significant association with shorter RFS. The latter has been reported in both before the imatinib [177, 178] ] and during the imatinib era [21]. Partly, there is data from 80 Ph+ ALL patients treated with imatinib, which was followed by alloHSCT in 60 of them. In fact it was found that the 2-year RFS for those who had undergone alloHSCT during CR1 was 62.6±7.5% compared to 62.1±12.3% for those who had not undergone alloHSCT. When alloHSCT was considered as a time-dependent covariant, it was shown to have no significant effect on RFS. On the other hand, a statistically significant negative impact on RFS for +der(22)t(9;22) and 9p abnormalities (p<0.001 and p<0.005) [21] was revealed, although it had not been demonstrated earlier [204].

Conclusions and future directions

The study of patients with Ph+ leukemias allowed a clarification of many sides of the nature and pathogenesis of leukemias [127, 128], and helped to develop new therapeutic approaches [208, 209]. The treatment of these disorders was partly revolutionized with TKIs. As a result, nowadays the vast majority of the patients with CML can be treated without alloHSCT. As far as HSCT is concerned, this must be reserved for those CML patients who become resistant to TKIs. The main reason for the resistance formation appears is considered to be mutations of BCR-ABL KD, primarily T315I. For achieving effect in relapsed after HSCT patients may be effectively used DLI which is the ideal approach for treating these CML patients [164].

In contrast to CML, alloHSCT is the only known curative modality for patients with Ph+ ALL under 55 years old. Naturally, it must be coupled by high dose chemotherapy and TKIs before transplantation [157, 170]. If such therapy is unsuccessful, testing for BCR-ABL domain mutations is necessary. Besides other prognostic factors, the following are considered to be important: a) additional chromosome changes, including the 2nd Ph-chromosome and 9p abnormalities; b) deletion of genes (i.e., IKAROS) needed for natural differentiation of B-cells; c) some cryptic chromosome changes; and d) micro-deletions of many important genes, which respond for natural differentiation of lymphoid and myeloid hematopoietic cells. The latest  investigations appear to be directed onto: a) the development of new techniques of mutation status testing;  b) the active introduction into clinical practice of TKIs of second- and third-lines; c) the further elucidation of mutated genes’ participation in both pathogenesis and resistance formation to treatment of Ph+ leukemias. As a result, one can expect that discoveries in these regions will allow the development of a concepts for target therapy of Ph+ leukemias, enabling more effective treatment than ever before.

References

1. Nowell PC, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497-9.

2. Rowley JD. Letter: A new consistent chromosome abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290-3.

3. Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96:3343-56.

4. Advani AS, Penderqast AM. Bcr-Abl variants: Biological and clinical aspects. Leuk Res. 2002;26:713-20. doi: 10.1016/S0145-2126(01)00197-7.

5. Pane F, Intrieri M, Quintarelli C, et al. BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations. Oncogene. 2002;21:8652-67.

6. Ottmann O, Dombret H,  Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007;110:2309-15. doi: 10.1182/blood-2007-02-073528.

7. Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.  Blood. 1996;88:2375-84.

8. Secker-Walker LM, Morgan GJ, Min T, et al. Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophils. Report of two cases. Cancer Genet Cytogenet. 1992;58:29-34. doi:10.1016/j.leukres.2005.06.003.

9. Alimena G, Cedrone M, Nanni M, et al. Acute leukemia presenting a variant Ph chromosome with p190 expression, dup 3q and -7, developed after malignant lymphoma treated with alkilating agents and topoisomerase II inhibitors. Leukemia. 1995;9:1483-6. pmid: 7658716.

10. Mitani K, Sato Y, Tojo A, et al. Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein. Br J Haematol. 1990;76:221-5. pmid: 2094324.

11. Martiat P, Meccucci C, Nizet Y, et al. P190 BCR/ABL transcript in a case of Philadelphia-positive multiple myeloma. Leukemia. 1990;4:751-4. pmid: 2232886.

12. Verhoef G, Meens P, Stul M, et al. Cytogenetic and molecular studies of the Philadelphia translocation in myelodysplastic syndrome. Report of two cases and review of the literature. Cancer Genet Cytogenet. 1992;59:161-6.

13. Keung YK, Beaty M, Powell BL, et al. Philadelphia chromosome positive myelodysplastic syndrome and acute myeloid leukemia – retrospective study and review of literature. Leuk Res. 2004;28:579-86. doi: 10.1016/j.leukres.2003.10.027.

14. Stoll DB, Peterson P, Exten R, et al. Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome. Am J Hematol. 1988;27:77-83. pmid: 3422539.

15. Martiat P, Ifrah N, Rassool F, et al. Molecular analysis of Philadelphia positive essential thrombocythemia. Leukemia. 1989;3:563-5. pmid: 2747291.

16. Cervantes F, Urbano Ispizua A, Villamor N, et al. Ph-positive chronic myeloid leukemia mimicking essential thrombocythemia and terminating into megakaryoblastic blast crisis: Report of two cases with molecular studies. Leukemia. 1993;7:327-30. pmid: 8426485.

17. Pane F, Frigeri F, Sindona M, et al. Neutrophilic-chronic myelogenous leukemia: A distinct disease with a specific molecular marker (BCR-ABL with c3a2 junction). Blood. 1996;88:2410-4.

18. Dorshkind K, Witte ON. Linking the hematopoietic microenvironment to imatinib-resistant Ph+ B-ALL. Genes Dev. 2007;21:2249-52. doi: 10.1101/gad.1600307.

19. Piccaluga PP, Paolini S, Martinelli G. Tyrosine kinase inhibitors for the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Cancer. 2007;110:1178-86. doi: 10.1002/cncr.22881.

20. Melo JV, Chuah C. Novel agents in CML therapy: tyrosine kinase inhibitors and beyond. Hematology Am Soc Hematol Educ Program. 2008;427-35.

21. Yanada M, Takeuchi J, Sugiura I, et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica. 2008;93:287-90. doi:10.3324/haematol.11891.

22. Nashed AL, Rao KW, Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagnostics. 2003;5:63-72.

23. Qiu H, Miao K, Wang R, et al.  The application of fluorescence in situ hybridization in detecting chronic myeloid leukemia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009;26:207-10. Chinese. pmid: 19350518.

24. Virgili A, Brazma D, Reid A, et al. FISH mapping of Philadelphia negative BCR/ABL I positive CML. Mol Cytogenetics. 2008;1:755-8. doi: 10.1186/1755-8166-1-14.

25. Hardling M, Wei Y, Palmqvist L, et al.  Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate. Med Oncol. 2004;21:349-58. doi: 10.1385/MO:21:4:349.

26. Doi Y, Sasaki D, Terada C, et al. High-resolution melting analysis for a reliable and two-step scanning of mutations in the tyrosine kinase domain of the chimerical bcr-abl gene. Int J Hematol. 2009 May 23. [Epub ahead of print]. doi: 10.1007/s12185-009-0337-y.

27. Jones D, Kamel-Reid S, Bahler D, et al. Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia. A report of the association for molecular pathology. J Mol Diagnostics. 2009;11:4-11. pmid: 19095773.

28. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12:7374-9. doi: 10.1158/1078-0432.CCR-06-1516.

29. Soverini S, Colarossi S, Gnani A, et al. Resistance to dasatinib in Philadelphia-positive leukemia patients is mainly mediated by the presence or the selection of mutations at residues 315 and 317 in the Bcr-Abl kinase domain. Haematologica. 2007;109:401-4. doi: 10.3324/haematol.10822.

30. Soverini S, Iacobucci I, Baccarani M, and Martinelli G. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. Haematologica. 2007;92:437-9. doi: 10.3324/haematol.11248.

31. Ernst T, Erben P, Miller M, et al. Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib. Haematologica. 2008;93:186-92. doi: 10.3324/haematol.11993.

32. Jones D, Thomas D, Yin CC, et al. Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors. Cancer. 2008;113:985-94.

33. Jones D, Luthra R, Cortes J, et al.  BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome–positive leukemias. Blood. 2008;112:5190-2. pmid: 18809762.

34. Yeoh EJ, Ross ME, Shurtleff SA, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1:133-43. doi: 10.1016/S1535-6108(02)00032-6.

35. Cimino G, Pane F, Elia M, et al. The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. Haematologica. 2006;91:377-80.

36. Burmeister T, Schwartz S, Taubald A, et al. Atypical BCR-ABL mRNA transcripts in adult acute lymphoblastic leukemia. Haematologica. 2007;92:1699-702. doi: 10.3324/haematol.11737.

37. Ohsaka A, Shina S, Kobayashi M, et al. Philadelphia chromosome-positive chronic myeloid leukemia expressing p190(BCR-ABL). Intern Med. 2002;41:1183-7.

38. Jiang DZ, Chen ZM, Lou JY, et al. Cytogenetic and molecular analysis of 1193 cases with chronic myeloid leukemia Zhonghua Xue Ye Xue Za Zhi. 2007;28:1-5. Сhinese. pmid: 17649716.

39. Dhingra K, Talpaz M, Kantarjian H, et al. Appearance of acute leukemia-associated P190 BCR-ABL in chronic myelogenous leukemia may correlate with disease progression. Leukemia. 1991;5:191-5. pmid: 2013978.

40. Melo JV, Myint H, Galton DA., and Goldman JM.  P190BCR-ABL chronic myeloid leukemia: The missing link with chronic myelomonocytic leukemia? Leukemia. 1994;8:208-11. pmid: 8289491.

41. Elliott SL, Taylor KM, Taylor DL, et al. Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location. Leukemia. 1995;9:946-50. pmid: 7596182.

42. Shepherd P, Suffolk R, Halsey J, et al. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukemia: No correlation with clinical features, cytogenetic response, duration of chronic phase or survival. Br J Haematol. 1995;89:546-54. pmid: 7734353.

43. Rozman C, Urbano Ispizua A, Cervantes F, et al. Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia. Leukemia. 1995;9:1104-7. pmid: 7596178.

44. Kutsev S, Velchenko M. The role of BCR-ABL gene mutation analysis in the optimization of target therapy of chronic myeloid leukemia. Clin Oncohematol. 2008;1:190-9. Russian.

45. Al-Ali HK, Leiblein S, Kovacs I, et al. CML with an e1a3 BCR-ABL fusion: rare, benign, and a potential diagnostic pitfall. Blood. 2002;100:1092-3.

46. Snyder DS, McMahon R, Cohen SR, et al. Chronic myeloid leukemia with an e13a3 BCR-ABL fusion: benign course responsive to imatinib with an RT-PCR advisory. Am J Hematol. 2004;75:92-5. doi: 10.1002/ajh.10456.

47. Lee JJ, Kim HJ, Lee S, et al. Imatinib induces a cytogenetic response in blast crisis of interferon failure chronic myeloid leukemia patients with e19a2 BCR-ABL transcripts. Leukemia. 2004;18:1539-40. doi: 10.1038/sj.leu.2403454.

48. Popovici C, Cailleres S, David M, et al. E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib. Leuk Lymphoma. 2005;46:1375-7. doi: 10.1080/10428190500138138.

49. Grégoire M-J, Latger-Cannard V, Staal A, et al. Identification of an acute basophilic leukemia carrying a rare e6a2 BCR-ABL transcript. Acta Haematol. 2006;116;216-8. doi: 10.1159/000094686.

50. Colla S, Sammarelli G, Voltorini S, et al. e6a2 BCR-ABL transcript in chronic myeloid leukemia: is it associated with aggressive disease? Haematologica. 2004;89:611-3.

51. Hochhaus A, Reiter A, Sklandy H, et al. A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome negative chronic myelogenous leukemia. Blood. 1996;88:2236-40.

52. Gleiβner B, Gökbuget N, Bartram CR, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002;99:1536–43.

53. Elia LI, Manchini M, Moleti L, et al. A multiplex reverse transcriptase-polymerase chain reaction strategy for the diagnostic molecular screening of chimeric genes: a clinical evaluation on 170 patients with acute lymphoblastic leukemia. Haematologica. 2003;88:275-9.

54. Juric D, Lacayo NJ, Ramsey MC, et al. Differential gene expression patterns and interaction networks in BCR-ABL-positive and –negative adult acute lymphoblastic leukemias. J Clin Oncol. 2007;25:1341-9. doi: 10.1200/JCO.2006.09.3534.

55. Schlieben S, Borkhardt A, Reinisch I, et al. Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05–92. Leukemia. 1996;10:957-63. pmid: 8667652.

56. Uckun FM, Nachman JB, Sather HN, et al. Clinical significance of Philadelphia chromosome-positive pediatric acute lymphoblastic leukemia in context of contemporary intensive therapies: a report from the children’s cancer group. Cancer. 1998;83:2030–9. doi: 10.1002/(SICI)1097-0142(19981101)83:9<2030::AID-CNCR21>3.0.CO;2-Q.

57. Scheuring US, Pfeifer H, Wassmann B, et al. Methodologic and biological variability of quantitative real-time polymerase chain reaction analysis of Bcr-Abl expression in Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2003;88:1074-5.

58. Rotoli B, Pane F, Salvatore F, et al. The e19a2 bcr/abl breakpoint in acute lymphoblastic leukemia. Br J Haematol. 2000;110:493-6.

59. Wilson GA, Van den Berghe EA, Politt RC, et al. Are aberrant BCR-ABL transcripts more common than previously thought? Br J Hematol. 2000;111:1109-11.

60. Wassmann B, Gökbuget N, Scheuring UJ, et al. A randomized multicenter open label phase II study to determine the safety and efficacy of induction therapy with imatinib (Glivec, formerly STI571) in comparison with standard induction chemotherapy in elderly (>55 years) patients with Philadelphia chromosome-positive (Ph+/BCR-ABL+) acute lymphoblastic leukemia (ALL) (CSTI571ADE10). Ann Hematol. 2003;82:716-20.

61. Talpaz M, Shah N, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia-chromosome-positive leukemias. N Engl J Med. 2006;354:2531-41.

62. Volkova MA. New possibilities in the therapy of the chronic myelocytic leukemia: dasatinib. Clin Onkohematol. 2008;1:218-26. Russian.

63. Tiribelli M, Sperotto A, Candoni A, et al. Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leukemia Res. 2009;33:174-7.

64. Schultz KR, Pullen DJ, Sather HN, et al. Risk and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG). Blood. 2007;109: 926-35. doi: 10.1182/blood-2006-01-024729.

65. Secker-Walker LM, Craig JM. Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review. Leukemia. 1993;7:147–51. pmid: 8426467.

66. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of BCR-ABL positive cells. Nat Med. 1996;2:561-6. pmid: 8616716.

67. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New Engl J Med. 2001;344:1031-7.

68. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-42.

69. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of imatinib therapy for newly diagnosed chronic leukemia in chronic-phase shows sustained responses and high overall survival. N Engl J Med. 2006;355:2408-17.

70. Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood. 2007;110:2828-37. doi: 10.1182/blood-2007-04-038943.

71. Kantarjian HM, Cortes J, O’Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome positive chronic myelogenous leukemia in blast phase. Blood. 2002;99:3547-53.

72. Kantarjian HM, O’Brien S, Cortes JE, et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood. 2002;100:1590-5.

73. Kantarjian HM, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2003;346:645-52.

74. Kantarjian HM, Talpaz M, O’Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101:473-5. doi: 10.1182/blood-2002-05-1451.

75. Kantarjian HM, Talpaz M, O’Brien S, et al. Survival benefit with imatinib mesylate versus-interferon alfa-based regimens in newly diagnosed chronic phase chronic myelogenous leukemia. Blood. 2006a;108:1835-40.

76. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100:1965-71. doi: 10.1182/blood-2001-12-0181.

77. Radojkovic M, Ristic S, Pavlovic S, Colovic M. Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis. Leuk Res. 2009;33:10-2. doi: 10.1016/j.leukres.2008.10.028.

78. Roy L, Guilhot J, Krahnke T, et al. Survival advantage with imatinib compared to the combination interferon-α plus cytarabine in chronic phase CML: historical comparison between two phases III trials. Blood. 2006;108:1478-84. doi: 10.1182/blood-2006-02-001495.

79. de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood. 2007;109:1408-13. doi: 10.1182/blood-2006-03-011908.

80. Vignetti M, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) LAL201-B protocol. Blood. 2007;109:3676-8. doi: 10.1182/blood-2006-10-052746.

81. Zaritsky AYu, Lomaia EG, Vinogradova OYu, et al. Prognosis factors in Imatinib mesylate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia. Ther Arkh. 2007;79(8):17-22. Russian.

82. Palandri F, Iacobucci I, Martinelli G, et al. Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, Philadelphia-positive chronic myeloid leukemia: The GIMENA Working Party on CML. J Clin Oncol. 2008;26:106-11. doi:  10.1200/JCO.2007.13.2373.

83. Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112:4808-17.

84. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99:1928-37.

85. Palandri F, Castagnetti F, Testoni N, et al. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. Haematologica. 2008;93:1792-6. doi: 10.3324/haematol.13068.

86. Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99:3530-9.

87. Kantarjian HM, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354:2542-51.

88. De Lavallade H, Apperley JF, Khorashad JK, et al. Imatinib for newly diagnose patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358-63.

89. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the managements of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809-20. doi: 10.1182/blood-2006-02-005686.

90. Brave M, Goodman V, dvardas Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res. 2008;14:352-9. doi: 10.1158/1078-0432.CCR-07-4175.

91. Steinberg M. Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther. 2007;29:2289-308. doi: 10.1016/j.clinthera.2007.11.005.

92. Keam SJ. Dasatinib: in chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. BioDrugs. 2008;22:59-69. pmid: 18215092.

93. Le Coutre P, Ottmann OG, Giles F, et al. Nilotinib (formally AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008;111:1834-9. doi: 10.1182/blood-2007-04-083196.

94. Castagnetti F, Palandri F, Amabile M, et al. Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party. Blood. 2009;113:3428-34. doi: 10.1182/blood-2007-08-103499.

95. Palandri F, Castagnetti F, Alimena G, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up. Haematologica. 2009;94:205-212. doi: 10.3324/haematol.13529.

96. Tokarski JS, Newitt JA, Cheng CY, et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res. 2006;66:5790-7. 97. Guilhot F, Apperley J, Kim D-W, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or- intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143-50.

97. Guilhot F, Apperley J, Kim D-W, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or- intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:4143-50. doi: 10.1182/blood-2006-09-046839.

98. Jabbour E, Kantarjian H, Jones D, et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood. 2008;112:53-5. doi: 10.1182/blood-2007-11-123950.

99. Jabbour E, Kantarjian HM, Jones D, et al.  Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after  therapy with tyrosine kinase inhibitors. Blood. 2008;112:4839-42. doi: 10.1182/blood-2008-04-149948.

100. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004; 103:4396-407. doi: 10.1182/blood-2003-08-2958.

101. Thomas D.A. Philadelphia chromosome–positive acute lymphocytic leukemia: a new era of challenges. Hematology Am Soc Hematol Educ Program Book. 2007:435-43.

102. Towatari M, Yanada M, Usui N, et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood. 2004;104:3507-12. doi: 10.1182/blood-2004-04-1389.

103. Ottmann OG, Wassmann B. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology. Am Soc Hematol Educ Program. 2005:118-22.

104. Yanada M, Naoe T. Imatinib combined chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: major challenges in current practice. Leuk Lymphoma. 2006;47:1474-53. doi: 10.1080/10428190600634085.

105. Yanada M, Takeuchi J, Sugiura I, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24:460-6.

106. Wassmann B, Pfeifer H, Scheuring UJ, et al. Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with imatinib. Blood. 2004;103:1495-8. doi: 10.1182/blood-2003-01-0154.

107. Lee S, Kim Y-J, Min C-K, et al.  The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2005;105:3449-57. doi: 10.1182/blood-2004-09-3785.

108. Wassmann B, Pfeifer H, Stadier M, et al. Early molecular response to post transplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005;106:458-63. doi: 10.1182/blood-2004-05-1746.

109. Wassmann B, Pfeifer H, Gökbuget N, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2006;108:1469-77. doi: 10.1182/blood-2005-11-4386.

110. Ohno R. Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Curr Oncol Rep. 2008;10:379-87. pmid: 18706265.

111. Scheuring US, Pfeifer H, Wassmann B, et al. Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571). Blood. 2003;101:85-90. doi: 10.1182/blood-2002-02-0360.

112. Ottmann OG, Wassmann B, Pfeifer H, et al. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2007;109:2068-76.

113. Apperley JF. Mechanisms of resistance to imatinib in chronic myeloid leukemia. Part I. Lancet Oncol. 2007;8:1018-29. pmid: 17976612.

114. Khorashad JS, de Lavallade H, Apperley JF, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008;26:4806-13. pmid: 18645191.

115. Saglio G, Ulishiani S, Bosa M, et al. New therapeutic approaches and prognostic factors in chronic myeloid leukemia. Leuk Lymphoma. 2008;49:625-8. doi: 10.1080/10428190801896210.

116. Verma D, Fava C, Kantarjian H, Cortes J. Complexity of BCR-ABL kinase domain mutations during the course of therapy with tyrosine kinase inhibitors in chronic myeloid leukemia. Am J Hematol. 2009;84:256-7. doi: 10.1002/ajh.21366.

117. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20:1767-73. doi: 10.1038/sj.leu.2404318.

118. Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program. 2007:376-83.

119. Al-Ali HK, Heinrich MC, Lange T, et al.  High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J. 2004;5:55-60.

120. Lahaye T, Riehm B, Berger U, et al.  Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer. 2005;103:1659-69. doi: 10.1002/cncr.20922.

121. Quintas-Cardama A, Kantarjian H, Jones D, et al. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood. 2007;109:497-9. doi: 10.1182/blood-2006-07-035493.

122. Cortes J, Rousselot P, Kim D, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007;109:3207-13. doi: 10.1182/blood-2006-09-046888.

123. Shah NP, Skaggs BJ, Branford S, et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J Clin Invest. 2007;117:2562-9. doi: 10.1172/JCI30890.

124. Soverini S, Martinelli G, Colarossi S, et al. Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL. Lancet Oncol. 2007;8:273-4. doi: 10.1016/S1470-2045(07)70078-5.

125. Jabbour E, Kantarjian HM, Jones D, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood. 2008;112:4839-42. doi: 10.1182/blood-2008-04-149948.

126. Giles FJ, Cortes J, Jones D, et al. VK-047, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood. 2007;109:500-2. doi: 10.1182/blood-2006-05-025049.

127. Nicolini FE, Corm S, Lĕ QH, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia. 2006;20:1061-6. doi: 10.1038/sj.leu.2404236.

128. Hochhaus A, Kantarjian H, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic- phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109:2303-9. doi: 10.1182/blood-2006-09-047266.

129. Zonder JA, Pemberton P, Brandt H, et al. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to imatinib treatment. Clin Cancer Res. 2003;9:2092-7.

130. Chu S, Xu H, Snyder DS, et al. Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood. 2005;105:2093-8. doi: 10.1182/blood-2004-03-1114.

131. Sherbenou DW, Wong MJ, Humayun A, et al. Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic responses to imatinib. Leukemia. 2007;21:489-93.

132. Hughes T. ABL kinase inhibitor therapy for CML: baseline assessments and response monitoring. Hematology Am Soc Hematol Educ Program Book. 2006:211-8.

133. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28-37. doi: 10.1182/blood-2006-01-0092.

134. Pfeifer H, Wassmann B, Pavlova A, et al. Kinase domain mutations of BCR-ABL frequency precede Imatinib-based therapy and give to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2007;110:727-34. doi: 10.1182/blood-2006-11-052373.

135. Passweg JR, Walker I, Sobocinski KA, et al. Validation and extension of the EBMT risk score for patients with chronic myeloid leukemia (CML) receiving allogeneic haemopoietic stem cell transplants. Br J Haematol. 2004;125:613-20.

136. Sullivan KM, Weiden PL, Storb R, et al.  Influence of acute and chronic graft-versus-host disease on relapse and survival after bone transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.  Blood. 1989;73:1720-8.

137. Serrano J, Roman J, Sanchez J, et al.  Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210 (BCR-ABL) and p190 (BCRABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190 (BCR- ABL) detection precedes cytogenetic relapse. Blood. 2000;95:2659–65.

138. Collins RH, Roggers ZR, Bennett M, et al. Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: Apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant. 1992;10:391-5. pmid: 1422499.

139. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood. 1995;86:2041-50.

140. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371-83.

141. Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes  for relapse of chronic myeloid leukemia after bone marrow transplantation: Separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 1995;86:1261-8.

142. Collins RH, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433-44. pmid: 9053463.

143. Dazzi F, Szydio RM, Goldman JM. Donor lymphocyte infusion for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: Where we now stand. Exp Hematol. 1999;27:1477-86.

144. Dazzi F, Szydio RM, Craddock C, et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood. 2000;95:67-71.

145. Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: Prognostic relevance of the initial cell dose. Blood. 2002;100:397-405.

146. Olavarria E, Ottman OG, Deininger M, et al. Chronic Leukemia Working Party of the European Group of Bone and Marrow Transplantation (EBMT). Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2003;17:1707-12.

147. Olavarria E, Siddique Sh, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110:4614-7. doi: 10.1182/blood-2007-04-082990.

148. Tomblyn M, Lazarus HM. Donor lymphocyte infusion: the long and winding road: how should it be traveled? Bone Marrow Transplant. 2008;42:569-79. doi: 10.1038/bmt.2008.259. 

149. DeAngelo DJ, Hochberg EP, Alyes EP, et al. Extended follow-up of patients treated with imatinib mesylate (Gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation. Durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease. Clin Cancer Res. 2004;10:5065-71. doi: 10.1158/1078-0432.CCR-03-0580.

150. Duniop LC, Powles R, Singhal S, et al. Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant. 1996;17:365-9. pmid: 8704688.

151. Snyder DS, Nademanee AP, O’Donnell MR, et al. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999;13:2053-8. pmid: 10602428.

152. Laport GG, Alvarnas JC, Palmer JM, et al. Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractioned total body irradiation-etoposide regimen. Blood. 2008;112:903-9. doi: 10.1182/blood-2008-03-143115.

153. Hoelzer D, Gökbuget N, Ottmann OG. Targeted therapies in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Semin Hematol. 2002;39:32-7. pmid: 12447850.

154. Avivi I, Goldstone AH. Bone marrow transplant in Ph+ ALL patients. Bone Marrow Transplant. 2003;31:623-32. doi: 10.1038/sj.bmt.1703899.

155. Fielding AK, Goldstone AH. Allogeneic hematopoietic stem cell transplant in Philadelphia-positive acute lymphoblastic leukemia. Bone Marrow Transplant. 2008;41:447-53. doi: 10.1038/sj.bmt.1705904.

156. Bachanova V, Weisdorf D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant. 2008;41:455-64. doi: 10.1038/sj.bmt.1705889.

157. Lee S, Kim YJ, Chung NG, et al. The extent of minimal residual disease reduction after the first 4-week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2009;115:561-70. doi: 10.1002/cncr.24026.

158. Forman SJ, O’Donnell MR, Nademanee AP, et al. Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1987;70:587-8.

159. Barrett AJ, Horowitz MM, Ash RC, et al. Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1992;79:3067-70.

160. Arico M, Valsecchi MG, Camitta B, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med. 2000;342:998-1006.

161. Dombert H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia – results of the prospective multicenter LALA-94 trial. Blood. 2002;100:2357-66. doi: 10.1182/blood-2002-03-0704.

162. Esperou H, Boiron JM, Cayuela JM, et al. A potential graft-versus leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from the French Bone Marrow Transplantation Society. Bone Marrow Transplant. 2003;31:909-18. doi: 10.1038/sj.bmt.1703951.

163. Gupta V, Yi QL, Brandwei J, et al. The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison. Bone Marrow Transplant. 2004;33:397-404. doi: 10.1038/sj.bmt.1704368.

164. Goldstoune AH, Chopra R, Buck G, et al. The outcome of 267 Philadelphia positive adults in the International UKALLXII/ECOG E2993 study. Final analysis and the role of allogeneic transplant in those under 50 years [abstract]. Blood. 2003;102:80a.

165. Martin TG, Gajewski JL. Allogeneic stem cell transplantation for acute lymphocytic leukemia in adults: advances in the treatment of adult acute lymphocytic leukemia. Hematol Oncol Clin North Am. 2001;15:97-120.

166. Abou Mourad YR, Fernandez HF, Kharfan-Dabaja MA. Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Biol Blood Marrow Transplant. 2008;14:949-58.

167. Stein A, Forman SJ. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant. 2008;41:439-46. doi: 10.1038/bmt.2008.1.

168. Kovacsovics T, Maziarz R.T. Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of imatinib treatment on remission induction and allogeneic stem cell transplantation. Curr Oncol Rep. 2006;8:343-51. pmid: 16901395.

169. Carpenter PA, Snyder DS, Flowers ME. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007;109:2791-3. doi: 10.1182/blood-2006-04-019836.

170. Merante S, Colombo AA, Calatroni S, et al. Nilotinib restores long-term full-donor chimerism in Ph-positive acute lymphoblastic leukemia relapsed after allogeneic transplantation. Bone Marrow Transplant. 2009; Feb 9. [Epub ahead of print]. doi: 10.1038/bmt.2009.6.

171. Collins Jr RH, Goldstein S, Giralt S, et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 2000;26:769-74.

172. Kolb HJ, Schmid C, Barrett AJ, et al. Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 2004;103:767-76. doi: 10.1182/blood-2003-02-0342.

173. Choi SJ, Lee JH, Lee JH, et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy follower by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant. 2005;36:163-9.

174. Deiniger MW. Milestones and monitoring in patients with CML treated with imatinib. Hematology Am Soc Hematol Educ Program. 2008;419-26.

175. Goldman J. Monitoring minimal residual disease in BCR-ABL-positive chronic myeloid leukemia in the imatinib era. Curr Opin Hematol. 2005;12(1):33-9. pmid: 15604889.

176. Raanani P, Ben-Bassat I, Gan S, et al. Assessment of the response to imatinib in chronic myeloid leukemia patients: comparison between the FISH, multiplex and RT-PCR methods. Eur J Haematol. 2004;73:243-50. doi: 10.1111/j.1600-0609.2004.00287.x.

177. Schoch C, Schnittger S, Bursch S, et al. Comparison of chromosome banding analysis, interphase- and hyper metaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia. 2002;16:53-9.

178. Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR.  Methods Mol Med. 2006;125:69-92. pmid: 16502578.

179. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia. Blood Rev. 2006;20:29-41. doi: 10.1016/j.blre.2005.01.008.

180. Wang Y, Wu D, Sun A, et al. Allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in second chronic phase attained by imatinib after onset of blast crisis. Int J Hematol. 2008;87167-71. doi: 10.1007/s12185-008-0032-4.

181. Branford S, Cross NC, Hochhaus A, et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukemia. Leukemia. 2006;20:1925-30. doi: 10.1038/sj.leu.2404388.

182. Muller MC, Saglio G, Lin F, et al. An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007;92:970-3. doi: 10.3324/haematol.11172.

183. O’Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood. 2004;103:451-5. doi: 10.1182/blood-2003-02-0371.

184. Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood. 2004;104:2926-32. doi: 10.1182/blood-2004-03-1134.

185. Jabbour E, Kantarjian HM, Abruzzo LV, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2007;110:2991-5. doi: 10.1182/blood-2007-01-070045.

186. Martynkevich IS, Martynenko LS, Ivanova M.P, et al. Clonal evolution in Ph-positive CML Gleevec treated patients. Bulletin Hematol. 2007;3(1):30-4. Russian.

187. Machova Polakova K, Zmekova V, Rulcova J, et al. BCR-ABL mutations in chronic myeloid leukemia – Not only detection. Leukemia Lymphoma. 2008;49:1620-2.

188. Spinelli O, Peruta B, Tosi M, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. Haematologica. 2007;92:612-8. doi: 10.3324/haematol.10965.

189. Thörn I, Botling J, Hermansson M, et al. Monitoring minimal residual disease with flow cytometry, antigen-receptor gene rearrangements and fusion transcript quantification in Philadelphia-positive childhood acute lymphoblastic leukemia. Leuk Res. 2009;33:1047-1054. doi: 10.1016/j.leukres.2008.11.031.

190. Willis SG, Lange T, Demehri S, et al. High sensitivity detection of Bcr-ABL kinase domain mutations in imatinib-naïve patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood. 2005;106:2128-37. doi: 10.1182/blood-2005-03-1036.

191. Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood. 2008;112:4437-44. doi: 10.1182/blood-2008-06-162388.

192. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007;109:58-60. doi: 10.1182/blood-2006-03-011239.

193. Fava C, Kantarjian HM, Jabbour E, et al. Failure to achieve a complete hematologic response at the time of achievement of a major cytogenetic response with second generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood. 2009;00:00-00. doi: 10.1182/blood-2008-10-184960.

194. Jones LK, Saha V. Philadelphia positive acute lymphoblastic leukemia of childhood. Br J Haematol. 2005;130:489-500. doi: 10.1111/j.1365-2141.2005.05611.x.

195. Iacobucci I, Lonetti A, Cilloni D, et al. Identification of different Ikaros transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method. Haematologica. 2008;93:1814-21. doi: 10.3324/haematol.13260.

196. Iacobucci I, Lonetti A, Messa F, et al. Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance. Blood. 2008;112:3847-55. doi: 10.1182/blood-2007-09-112631.

197. Mullighan CG, Miller CB, Phillips LA, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453:110-4. doi: 10.1038/nature06866.

198. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360:470-80.

199. Georgopoulos K. Acute lymphoblastic leukemia – on the wings of IKAROS. N Engl J Med. 2009;360:524-6.

200. Rieder H, Ludwig WD, Gassmann W, et al. Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Br J Haematol. 1996;95:678-91. pmid: 8982045.

201. Thomas X, Thiebaut A, Olteanu N, et al. Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther. 1998;40:119-28. pmid: 9698220.

202. Wetzler M, Dodge RK, Mrozek K, et al. Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia: a study of the Cancer and Leukemia Group B. Br J Haematol. 2004;124:275-88.

203. Moormann AV, Harrison CJ, Buck GA, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALL111/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109:3189-97. doi: 10.1182/blood-2006-10-051912.

204. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008;111:2563-72. doi: 10.1182/blood-2007-10-116186.

205. Li Y, Qiu L, Zou D, Zhao Y, et al. Additional chromosomal abnormalities and their prognostic significance in adult Philadelphia-positive acute lymphoblastic leukemia: with or without imatinib in chemotherapy. Ann Hematol. 2009; Mar 10. [Epub ahead of print]. doi: 10.1007/s00277-009-0720-z.

206. Yanada M, Takeuchi J, Sugiura I, et al. Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. Haematologica. 2008;93:287-290. doi: 10.3324/haematol.11891.

207. Paulsson K, Cazier J-B, MacDougall F, et al. Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease. Proc National Acad Sci. 2008;105:6708-13.

208. Eiring AM, Neviani P, Santhanam R, et al. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood. 2008;111:816-28. doi: 10.1182/blood-2007-05-090472.

209. Laport GG, Alvarnas JC, Palmer JM, et al. Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation-etoposide regimen. Blood. 2008;112:903-9. doi: 10.1182/blood-2008-03-143115.

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Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена <i>ABL-BCR </i>и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph<sup>+</sup> ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph<sup>+</sup> ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена <i>ABL-BCR</i>, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph<sup>+</sup> лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей.  </p> <p class="bodytext">Одним из важных моментов большого успеха аллоТГСК при Ph<sup>+</sup> лейкозах является высокая чувствительность Ph<sup>+</sup> клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph<sup>+</sup> ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph<sup>+</sup> ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.</p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(284) "Ph-позитивные лейкозы в эру современной цитогенетики, молекулярной биологии, ингибиторов тирозин-киназ и трансплантации гемопоэтических стволовых клеток" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(284) "Ph-позитивные лейкозы в эру современной цитогенетики, молекулярной биологии, ингибиторов тирозин-киназ и трансплантации гемопоэтических стволовых клеток" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(284) 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"HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14137" ["VALUE"]=> array(2) { ["TEXT"]=> string(50) "<p>Николай Н. Мамаев</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(38) "

Николай Н. Мамаев

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14138" ["VALUE"]=> array(2) { ["TEXT"]=> string(4675) "<p class="bodytext">Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph<sup>+</sup>) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена <i>ABL-BCR </i>и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph<sup>+</sup> ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph<sup>+</sup> ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена <i>ABL-BCR</i>, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph<sup>+</sup> лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей.  </p> <p class="bodytext">Одним из важных моментов большого успеха аллоТГСК при Ph<sup>+</sup> лейкозах является высокая чувствительность Ph<sup>+</sup> клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph<sup>+</sup> ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph<sup>+</sup> ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(4511) "

Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph+) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена ABL-BCR и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph+ ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph+ ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена ABL-BCR, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph+ лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей. 

Одним из важных моментов большого успеха аллоТГСК при Ph+ лейкозах является высокая чувствительность Ph+ клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph+ ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph+ ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.

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Nikolay N. Mamaev

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St. Petersburg Pavlov State Medical University, St. Petersburg, Russia


Correspondence:
Nikolay N. Mamaev, Clinical-laboratory Diagnostics Chair, Cytogenetic Lab, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 198022, Russia
Phone: +7 (812) 233-12-43 (office) or +7 (812) 726-53-25 (home)
E-mail: nikmamaev@spam is badrambler.ru

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The review is devoted to the complex problems of modern cytogenetic and molecular diagnostics of Ph-positive leukemias, their treatment in era tyrosine kinase inhibitors and hematopoietic stem cell transplantation at the condition of cytogenetic and molecular monitoring.

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Nikolay N. Mamaev

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The review is devoted to the complex problems of modern cytogenetic and molecular diagnostics of Ph-positive leukemias, their treatment in era tyrosine kinase inhibitors and hematopoietic stem cell transplantation at the condition of cytogenetic and molecular monitoring.

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The review is devoted to the complex problems of modern cytogenetic and molecular diagnostics of Ph-positive leukemias, their treatment in era tyrosine kinase inhibitors and hematopoietic stem cell transplantation at the condition of cytogenetic and molecular monitoring.

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St. Petersburg Pavlov State Medical University, St. Petersburg, Russia


Correspondence:
Nikolay N. Mamaev, Clinical-laboratory Diagnostics Chair, Cytogenetic Lab, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 198022, Russia
Phone: +7 (812) 233-12-43 (office) or +7 (812) 726-53-25 (home)
E-mail: nikmamaev@spam is badrambler.ru

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St. Petersburg Pavlov State Medical University, St. Petersburg, Russia


Correspondence:
Nikolay N. Mamaev, Clinical-laboratory Diagnostics Chair, Cytogenetic Lab, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 198022, Russia
Phone: +7 (812) 233-12-43 (office) or +7 (812) 726-53-25 (home)
E-mail: nikmamaev@spam is badrambler.ru

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Николай Н. Мамаев

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Николай Н. Мамаев

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Mamaev" ["LINK_ELEMENT_VALUE"]=> bool(false) } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14138" ["VALUE"]=> array(2) { ["TEXT"]=> string(4675) "<p class="bodytext">Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph<sup>+</sup>) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена <i>ABL-BCR </i>и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph<sup>+</sup> ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph<sup>+</sup> ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена <i>ABL-BCR</i>, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph<sup>+</sup> лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей.  </p> <p class="bodytext">Одним из важных моментов большого успеха аллоТГСК при Ph<sup>+</sup> лейкозах является высокая чувствительность Ph<sup>+</sup> клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph<sup>+</sup> ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph<sup>+</sup> ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(4511) "

Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph+) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена ABL-BCR и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph+ ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph+ ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена ABL-BCR, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph+ лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей. 

Одним из важных моментов большого успеха аллоТГСК при Ph+ лейкозах является высокая чувствительность Ph+ клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph+ ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph+ ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.

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Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph+) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена ABL-BCR и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph+ ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph+ ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена ABL-BCR, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph+ лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей. 

Одним из важных моментов большого успеха аллоТГСК при Ph+ лейкозах является высокая чувствительность Ph+ клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph+ ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph+ ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.

" } } } [9]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(2) "47" ["~IBLOCK_SECTION_ID"]=> string(2) "47" ["ID"]=> string(3) "999" ["~ID"]=> string(3) "999" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["~NAME"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "07/26/2017 03:40:58 pm" ["~TIMESTAMP_X"]=> string(22) "07/26/2017 03:40:58 pm" ["DETAIL_PAGE_URL"]=> string(116) "/en/archive/tom-1-nomer-4/forum/nauchnaya-statya-na-angliyskom-yazyke-o-chem-stoit-podumat-pered-otpravkoy-rukopisi/" ["~DETAIL_PAGE_URL"]=> string(116) "/en/archive/tom-1-nomer-4/forum/nauchnaya-statya-na-angliyskom-yazyke-o-chem-stoit-podumat-pered-otpravkoy-rukopisi/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(16495) "

Level of research

At first sight it seems evident that the decision of the editorial board to publish a given RA manuscript should rest primarily on the novelty of the data presented. This is the case for the majority of Russian researchers and also – most likely – for many Russian–language journals, for which novelty level is considered to be the key criterion for a manuscript’s fate. However, for English–language journals the purely phenomenological aspect of a study – particularly the introduction of a new finding – as well as the confirmation, alteration, or even complete re-evaluation of a well-known one may not prove to be the only merit to be taken into consideration; convincing evidence, documents, and the use of recognized techniques are also needed. Equally valuable is a clearly expressed interpretation of the facts and events in accordance with the system of previously documented data in the given science domain. Weak factual confirmation of new findings – which result from obsolete equipment – and insufficient, poorly arranged arguments – caused by the lack of domestic programs specialized in scientific language – are the most likely reasons why my compatriots’ studies in the fields of biology and medicine are so infrequently published in – with the exception of the Commonwealth of Independent States – foreign journals. When they are published, it is usually in collaboration with a team of foreign scientists as co-authors. An example of this preference for exclusive validity of methodical validation and theoretical interpretation might be apoptosis – programmed cell death. The phenomenon itself was introduced, understood on the whole, and named around three decade ago [2, 3] with strong subsequent confirmation in thousands of papers. Nevertheless, the 2002 Nobel Prize in Physiology or Medicine was awarded to neither the pioneers nor their numerous followers, but solely to three outstanding researchers: Sydney Brenner, Robert Horvitz, and John Sulston. These three scientists succeeded in decoding the key features of the phenomenon at the molecular level, thus establishing its fundamental significance in a number of physiological and pathological processes. For a Russian scientist, such an outcome may seem unfair because of the apparent negligence of the right of priority that had dominated science for centuries. Today – due to increasingly tough competition, cases of mistakes and even forgeries – foreign journals – in spite of their deepest respect towards pioneers – take not only the priority of a new fact into consideration, but also its distinct parameters such as the power of verification and proper positioning within the circle of existing entities and beyond. At any rate, in both the leading – e.g. Nature, Science, PNAS – and less prestigious journals, an RA manuscript lacking solid factual proof and profound theoretical substantiation will most likely be rejected – with the utmost politeness – just after or even before peer reviewing. And one should not feel offended or much worse discriminated against. The fact is that no journal with the tacit support of the majority of scientists abroad would risk its reputation by issuing a product of mediocre quality. In other words, as far as science on the whole and RA manuscripts in particular are concerned, the better the refinement, the higher the price of the product. Just like in economy, there is a higher premium for efficiently processed materials as opposed to raw materials.  

Style

Here, this term denotes aspects such as specific sequence, relative volume, and the positioning of distinct content parts in a regular RA. In both Russian– and English–language foreign journals, the same sections of the RA are available with only their order varying. The practice of steady reading for many years permits me to draw a number of cautious conclusions concerning the major RA sections, emphasizing the characteristic features of the domestic and English–language models.

Title

Despite the heading – in both cases – invariably introducing RA contents on the whole, in Russian journals the title phrase can be excessively generalized and thereby vague due to such beginnings as “Certain peculiarities…” or “Clinical (biochemical, molecular biological) study (investigation, analysis) of…” Since each of the above items can include a host of variables, the reader may feel baffled as to the particular RA subject. In English–language titles such vagueness is not used. This allows a person to grasp not only the subject, but also the “zest” of the study. At this junction, a very efficient approach to the concise clarification of an RA’s contents by its title – used by about 15% English–language authors – appears to be the sub–division of the heading by the insertion of a colon – e.g., the subject of the study: the major conclusion and/or the author’s credo – or an interrogative form of the title – e.g., setting up the problem with the predictable solution. Furthermore, the humoristic elements and especially naturalistic and even risky turns [4-6] in the title of an RA is, to my opinion, more suitable for fiction rather than for topics of science. Despite genuine witticism of the vulgarity-free type [7], one can easily sacrifice these “garments” to follow the commonly accepted tradition of sheer clarity in an RA title without primitive tricks.

Introduction

This part of a typical English–language RA – apart from setting up the task, which Russian authors also do – incorporates the history of the problem, concisely and yet exhaustively scaled to the topic – a bit too laconic in the Russian case often due to space limitations for domestic journals – which is followed and finalized by а short – consisting only of a phrase or two – presentation of the main results. This approach has only been recently introduced into Russian articles but is sometimes clumsily applied. Having analyzed numerous papers in distinct areas of biology and medicine, I cannot help but derive the conclusion that English–language – unlike Russian–language published articles – offer educational possibilities, as well as the introduction of new findings. As a result, any researcher – or even a student with sufficient basic training – is able to understand a difficult and unfamiliar item, thus becoming more competent or at least intrigued by its novelty. How can such an effect be produced? Usually, the author begins the RA with a plain description of some well-studied – and thus comprehensible to the reader – data, which at first sight has a very distant relationship with the RA subject. The author then skillfully harmonizes and flavors the introduction with quotations before gradually concentrating on facts relevant to the problem in question, thus guiding the reader to the precise objective of the study. The brief conclusion reinforced by the mentioning of the technical aspect of the work not only shows its major achievement but also lets the potential reader determine whether the subject is worth further attention without having to look through the whole text. Therefore, it appears that a good RA should entail the roles of both presentation of new data and ideas plus the delivery of a mini-lecture, whereby the reader is assisted in the rapid absorption of knowledge, and the decision process regarding individual direction in further work. To my deepest regret, Russian authors – again presumably due to length restrictions – often make too steep a start, with the description of difficult – sometimes excessively sophisticated – concepts that are clear only to the authors themselves; naturally, this narrows the circle of readers and repels potential followers. Attempting such an approach for the submission of an RA to a foreign journal may result in either – luckily – severe criticism by peer reviewers, or – most likely – in refusal, with a not so subtle hint at incompetence.

Materials and methods. Results

These two sections in English–language journals are arranged and standardized so nicely that Russian authors face only one problem: to identify a particular prototype paper followed by inserting their data into the text in accordance with the selected template or templates. The authors’ concerns are to be free of suspicion that unsolicited borrowing had taken place. Its seems clear that the “happy ending” of such a strategy would equally depend on a worthwhile stock of RA-prototypes, the level of linguistic training in English, and the author in question’s morals.

Discussion

This part of the RA is by definition the most extensive section and also the most difficult one in the sense of both the author’s work and the reader’s comprehension. By rough estimates, the discussion in regular English–language papers may occupy as much as 40% of its whole length. However, in Russian journals – including the more respectable ones – that figure hardly exceeds 20%; subjects of interest are confined – as a rule – to short summarizing of the major findings, corroboration of the author’s accuracy and correctness, the use of rare quotations from other researchers with identical views – without mentioning dissident studies or their unrestrained criticism – which is all finalized by an optimistic conclusion that is invariably in favor of the author’s results and concepts. But where is the elaborate chain of the arguments – both for and against the author’s concept – with the acknowledgement of the imperfect techniques that were applied? Why are quotations so scarce in comparison to English–language RA manuscripts in which the discussion incorporates the vast majority of the references? And lastly, what prevents authors’ – after disclosing their readiness for further work – from outlining future studies’ subsequent designs? Those able to overcome the weak points and bridge the gaps that this paper has considered, will undoubtedly see for themselves to what extent such efforts are justified by enjoying the success of having their RA manuscripts published in an English–language journal.  

The ideas raised and discussed here are done so with the sole intention of expressing my individual points of view, which may be supplemented, and – either partially or wholly – altered by a more skillful and shrewd follower dedicated not only to scientific work, but also to the methods of adequately presenting research in English–language journals. The above phrase – apart from its evident sense – is offered in an attempt to exemplify the ethical approach to RA manuscripts adopted by the advanced scientific community.

Translation

This paper makes five key recommendations concerning the strategy of translating an RA manuscript into English.

• The translator’s knowledge of English grammar – its verbal forms in particular – should not be below the level of one of the best textbooks [8]. The following website lists various books that may prove to be helpful: http://www.senglish.narod.ru/books.html.

• Apart from a substantial vocabulary – 1500 words or more – specialized dictionaries – such as a medical dictionary – are necessary for a translator [9]. However, users may notice that such dictionaries can lack many contemporary words. Thus, it is advisable for the translator to initiate, compile and regularly replenish specific field reference notebooks.

• An even greater problem may be the lack of experience in correctly inserting key words into a given phrase or turn of phrase. If this is the case, the recently released Collins COBUILD dictionary on CD-ROM – which contains plenty of different phrases – might be the solution. Despite my own limited vocabulary [1], I found the manner in which topics are classified make searching for certain phrases or terms simple. Furthermore, I greatly approve of COBUILD 2003 and recommend its practical use due to its clear display of synonyms – subsequent editions have only succeeded in making the selection of synonyms a rather tedious procedure.

• A very effective approach in composing phrases and/or turns of phrase seems to be to search for other examples via the user’s files; each file contains 200–250 abstracts – or 2–3 MB – of English–language articles. Working with the Russian–language text, the person scans through the files by using the key English–language word – in conjunction with the Ctrl+F feature – until the most appropriate term or phrase is found. It is to be utilized by carefully adjusting and trimming the prototype into the final product. Two to three hundred full-length papers processed in the above manner can also be of great value.

• To what extent – if at all – can one rely upon a professional philologist as a potential translator of a Russian–language RA manuscript? Completely, provided the person has a high competence in both linguistics and the particular science the given text is dealing with. However, these two distinct skills rarely co-exist in a single individual. That is why the typical solution seems to be the more-or-less amateurish translation by a scientist – employing some of the DIY recommendations above – who is accustomed to regularly reading in English. It would then be the responsibility of a professional philologist to refine the text to a high-quality standard.

References

1. Nevorotin AI. Matrichnuy frazeologicheskiy sbornik. Posobie po napisaniu nauchnoy stati na angliyskom yazuke. SPb, SpezLit. 2001. Russian.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2.  

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Izrailevich EE, Kachalova KN. Prakticheskaya grammatika angliyskogo yazuka s uprazhneniyami i kluchami. SPb. Karo. 2007. 608 p. Russian.

9. Anglo-russkiy medizinskiy slovar (70000 terminov). 4-e izd., ster. Moskva. Russo. 2000. Russian.

" ["~DETAIL_TEXT"]=> string(16495) "

Level of research

At first sight it seems evident that the decision of the editorial board to publish a given RA manuscript should rest primarily on the novelty of the data presented. This is the case for the majority of Russian researchers and also – most likely – for many Russian–language journals, for which novelty level is considered to be the key criterion for a manuscript’s fate. However, for English–language journals the purely phenomenological aspect of a study – particularly the introduction of a new finding – as well as the confirmation, alteration, or even complete re-evaluation of a well-known one may not prove to be the only merit to be taken into consideration; convincing evidence, documents, and the use of recognized techniques are also needed. Equally valuable is a clearly expressed interpretation of the facts and events in accordance with the system of previously documented data in the given science domain. Weak factual confirmation of new findings – which result from obsolete equipment – and insufficient, poorly arranged arguments – caused by the lack of domestic programs specialized in scientific language – are the most likely reasons why my compatriots’ studies in the fields of biology and medicine are so infrequently published in – with the exception of the Commonwealth of Independent States – foreign journals. When they are published, it is usually in collaboration with a team of foreign scientists as co-authors. An example of this preference for exclusive validity of methodical validation and theoretical interpretation might be apoptosis – programmed cell death. The phenomenon itself was introduced, understood on the whole, and named around three decade ago [2, 3] with strong subsequent confirmation in thousands of papers. Nevertheless, the 2002 Nobel Prize in Physiology or Medicine was awarded to neither the pioneers nor their numerous followers, but solely to three outstanding researchers: Sydney Brenner, Robert Horvitz, and John Sulston. These three scientists succeeded in decoding the key features of the phenomenon at the molecular level, thus establishing its fundamental significance in a number of physiological and pathological processes. For a Russian scientist, such an outcome may seem unfair because of the apparent negligence of the right of priority that had dominated science for centuries. Today – due to increasingly tough competition, cases of mistakes and even forgeries – foreign journals – in spite of their deepest respect towards pioneers – take not only the priority of a new fact into consideration, but also its distinct parameters such as the power of verification and proper positioning within the circle of existing entities and beyond. At any rate, in both the leading – e.g. Nature, Science, PNAS – and less prestigious journals, an RA manuscript lacking solid factual proof and profound theoretical substantiation will most likely be rejected – with the utmost politeness – just after or even before peer reviewing. And one should not feel offended or much worse discriminated against. The fact is that no journal with the tacit support of the majority of scientists abroad would risk its reputation by issuing a product of mediocre quality. In other words, as far as science on the whole and RA manuscripts in particular are concerned, the better the refinement, the higher the price of the product. Just like in economy, there is a higher premium for efficiently processed materials as opposed to raw materials.  

Style

Here, this term denotes aspects such as specific sequence, relative volume, and the positioning of distinct content parts in a regular RA. In both Russian– and English–language foreign journals, the same sections of the RA are available with only their order varying. The practice of steady reading for many years permits me to draw a number of cautious conclusions concerning the major RA sections, emphasizing the characteristic features of the domestic and English–language models.

Title

Despite the heading – in both cases – invariably introducing RA contents on the whole, in Russian journals the title phrase can be excessively generalized and thereby vague due to such beginnings as “Certain peculiarities…” or “Clinical (biochemical, molecular biological) study (investigation, analysis) of…” Since each of the above items can include a host of variables, the reader may feel baffled as to the particular RA subject. In English–language titles such vagueness is not used. This allows a person to grasp not only the subject, but also the “zest” of the study. At this junction, a very efficient approach to the concise clarification of an RA’s contents by its title – used by about 15% English–language authors – appears to be the sub–division of the heading by the insertion of a colon – e.g., the subject of the study: the major conclusion and/or the author’s credo – or an interrogative form of the title – e.g., setting up the problem with the predictable solution. Furthermore, the humoristic elements and especially naturalistic and even risky turns [4-6] in the title of an RA is, to my opinion, more suitable for fiction rather than for topics of science. Despite genuine witticism of the vulgarity-free type [7], one can easily sacrifice these “garments” to follow the commonly accepted tradition of sheer clarity in an RA title without primitive tricks.

Introduction

This part of a typical English–language RA – apart from setting up the task, which Russian authors also do – incorporates the history of the problem, concisely and yet exhaustively scaled to the topic – a bit too laconic in the Russian case often due to space limitations for domestic journals – which is followed and finalized by а short – consisting only of a phrase or two – presentation of the main results. This approach has only been recently introduced into Russian articles but is sometimes clumsily applied. Having analyzed numerous papers in distinct areas of biology and medicine, I cannot help but derive the conclusion that English–language – unlike Russian–language published articles – offer educational possibilities, as well as the introduction of new findings. As a result, any researcher – or even a student with sufficient basic training – is able to understand a difficult and unfamiliar item, thus becoming more competent or at least intrigued by its novelty. How can such an effect be produced? Usually, the author begins the RA with a plain description of some well-studied – and thus comprehensible to the reader – data, which at first sight has a very distant relationship with the RA subject. The author then skillfully harmonizes and flavors the introduction with quotations before gradually concentrating on facts relevant to the problem in question, thus guiding the reader to the precise objective of the study. The brief conclusion reinforced by the mentioning of the technical aspect of the work not only shows its major achievement but also lets the potential reader determine whether the subject is worth further attention without having to look through the whole text. Therefore, it appears that a good RA should entail the roles of both presentation of new data and ideas plus the delivery of a mini-lecture, whereby the reader is assisted in the rapid absorption of knowledge, and the decision process regarding individual direction in further work. To my deepest regret, Russian authors – again presumably due to length restrictions – often make too steep a start, with the description of difficult – sometimes excessively sophisticated – concepts that are clear only to the authors themselves; naturally, this narrows the circle of readers and repels potential followers. Attempting such an approach for the submission of an RA to a foreign journal may result in either – luckily – severe criticism by peer reviewers, or – most likely – in refusal, with a not so subtle hint at incompetence.

Materials and methods. Results

These two sections in English–language journals are arranged and standardized so nicely that Russian authors face only one problem: to identify a particular prototype paper followed by inserting their data into the text in accordance with the selected template or templates. The authors’ concerns are to be free of suspicion that unsolicited borrowing had taken place. Its seems clear that the “happy ending” of such a strategy would equally depend on a worthwhile stock of RA-prototypes, the level of linguistic training in English, and the author in question’s morals.

Discussion

This part of the RA is by definition the most extensive section and also the most difficult one in the sense of both the author’s work and the reader’s comprehension. By rough estimates, the discussion in regular English–language papers may occupy as much as 40% of its whole length. However, in Russian journals – including the more respectable ones – that figure hardly exceeds 20%; subjects of interest are confined – as a rule – to short summarizing of the major findings, corroboration of the author’s accuracy and correctness, the use of rare quotations from other researchers with identical views – without mentioning dissident studies or their unrestrained criticism – which is all finalized by an optimistic conclusion that is invariably in favor of the author’s results and concepts. But where is the elaborate chain of the arguments – both for and against the author’s concept – with the acknowledgement of the imperfect techniques that were applied? Why are quotations so scarce in comparison to English–language RA manuscripts in which the discussion incorporates the vast majority of the references? And lastly, what prevents authors’ – after disclosing their readiness for further work – from outlining future studies’ subsequent designs? Those able to overcome the weak points and bridge the gaps that this paper has considered, will undoubtedly see for themselves to what extent such efforts are justified by enjoying the success of having their RA manuscripts published in an English–language journal.  

The ideas raised and discussed here are done so with the sole intention of expressing my individual points of view, which may be supplemented, and – either partially or wholly – altered by a more skillful and shrewd follower dedicated not only to scientific work, but also to the methods of adequately presenting research in English–language journals. The above phrase – apart from its evident sense – is offered in an attempt to exemplify the ethical approach to RA manuscripts adopted by the advanced scientific community.

Translation

This paper makes five key recommendations concerning the strategy of translating an RA manuscript into English.

• The translator’s knowledge of English grammar – its verbal forms in particular – should not be below the level of one of the best textbooks [8]. The following website lists various books that may prove to be helpful: http://www.senglish.narod.ru/books.html.

• Apart from a substantial vocabulary – 1500 words or more – specialized dictionaries – such as a medical dictionary – are necessary for a translator [9]. However, users may notice that such dictionaries can lack many contemporary words. Thus, it is advisable for the translator to initiate, compile and regularly replenish specific field reference notebooks.

• An even greater problem may be the lack of experience in correctly inserting key words into a given phrase or turn of phrase. If this is the case, the recently released Collins COBUILD dictionary on CD-ROM – which contains plenty of different phrases – might be the solution. Despite my own limited vocabulary [1], I found the manner in which topics are classified make searching for certain phrases or terms simple. Furthermore, I greatly approve of COBUILD 2003 and recommend its practical use due to its clear display of synonyms – subsequent editions have only succeeded in making the selection of synonyms a rather tedious procedure.

• A very effective approach in composing phrases and/or turns of phrase seems to be to search for other examples via the user’s files; each file contains 200–250 abstracts – or 2–3 MB – of English–language articles. Working with the Russian–language text, the person scans through the files by using the key English–language word – in conjunction with the Ctrl+F feature – until the most appropriate term or phrase is found. It is to be utilized by carefully adjusting and trimming the prototype into the final product. Two to three hundred full-length papers processed in the above manner can also be of great value.

• To what extent – if at all – can one rely upon a professional philologist as a potential translator of a Russian–language RA manuscript? Completely, provided the person has a high competence in both linguistics and the particular science the given text is dealing with. However, these two distinct skills rarely co-exist in a single individual. That is why the typical solution seems to be the more-or-less amateurish translation by a scientist – employing some of the DIY recommendations above – who is accustomed to regularly reading in English. It would then be the responsibility of a professional philologist to refine the text to a high-quality standard.

References

1. Nevorotin AI. Matrichnuy frazeologicheskiy sbornik. Posobie po napisaniu nauchnoy stati na angliyskom yazuke. SPb, SpezLit. 2001. Russian.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2.  

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Izrailevich EE, Kachalova KN. Prakticheskaya grammatika angliyskogo yazuka s uprazhneniyami i kluchami. SPb. Karo. 2007. 608 p. Russian.

9. Anglo-russkiy medizinskiy slovar (70000 terminov). 4-e izd., ster. Moskva. Russo. 2000. Russian.

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Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином <i>автор</i> обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал. </p>" ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["SECTION_META_TITLE"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" ["SECTION_META_KEYWORDS"]=> string(150) "Научная статья на английском языке: о чем стоит подумать перед отправкой рукописи" 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} ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14195" ["VALUE"]=> array(2) { ["TEXT"]=> string(45) "<p>А. И. Неворотин</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(33) "

А. И. Неворотин

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14202" ["VALUE"]=> array(2) { ["TEXT"]=> string(217) "<p>Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(205) "

Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14203" ["VALUE"]=> array(2) { ["TEXT"]=> string(3441) "<p class="bodytext">Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином <i>автор</i> обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3407) "

Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином автор обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал.

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Alexey Nevorotin

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14204" ["VALUE"]=> array(2) { ["TEXT"]=> string(74) "<p>I. P. Pavlov Medical University, St. Petersburg, Russia</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(62) "

I. P. Pavlov Medical University, St. Petersburg, Russia

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14208" ["VALUE"]=> array(2) { ["TEXT"]=> string(1846) "<p class="bodytext">The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term <i>author</i> will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1812) "

The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal.

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Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с <i>апоптозом</i> (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки. </p> <h3>Стиль</h3> <p class="bodytext"> Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями. </p> <h3>Заглавие</h3> <p class="bodytext"> Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков. </p> <h3>Введение </h3> <p class="bodytext"> Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность. </p> <h3>Материал и методика. Результаты</h3> <p class="bodytext"> В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка. </p> <h3>Обсуждение</h3> <p class="bodytext"> Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале. </p> <p class="bodytext"> Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе). </p> <h3>Перевод</h3> <p class="bodytext"> Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.<br> <br> •    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте <a href="http://www.senglish.narod.ru/books.html" target="_blank"><u>http://www.senglish.narod.ru/books.html</u></a><u>.</u> <br> <br> •    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности. <br> <br> •    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.<br> <br> •    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом. <br> <br> •    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала. </p> <h3>Литература</h3> <p class="bodytext"> 1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001. </p> <p class="bodytext"> 2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963. </p> <p class="bodytext"> 3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501. </p> <p class="bodytext"> 4. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0R-4M7CMHV-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a08a9319307df8c31ab91f8edb83231b" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004</u></a>. </p> <p class="bodytext"> 5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8. </p> <p class="bodytext"> 6. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSS-4183951-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5bbd5567c24ff8458d03ad14bd2c9ef8" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2</u></a>.  </p> <p class="bodytext"> 7. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33122/?tool=pubmed" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198</u></a>. </p> <p class="bodytext"> 8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр.  </p> <p class="bodytext"> 9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.<br> </p> <p class="bodytext"> 10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(26620) "

Уровень исследования

На первый взгляд представляется очевидным, что при решении редколлегии соответствующего журнала в пользу или против публикации рукописи НС, самым существенным критерием ценности результатов является новизна. Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с апоптозом (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки.

Стиль

Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями.

Заглавие

Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков.

Введение

Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность.

Материал и методика. Результаты

В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка.

Обсуждение

Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале.

Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе).

Перевод

Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.

•    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте http://www.senglish.narod.ru/books.html.

•    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности.

•    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.

•    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом.

•    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала.

Литература

1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр. 

9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.

10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999.

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Alexey Nevorotin

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Alexey Nevorotin

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The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal.

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The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal.

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I. P. Pavlov Medical University, St. Petersburg, Russia

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I. P. Pavlov Medical University, St. Petersburg, Russia

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А. И. Неворотин

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А. И. Неворотин

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"HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14203" ["VALUE"]=> array(2) { ["TEXT"]=> string(3441) "<p class="bodytext">Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином <i>автор</i> обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3407) "

Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином автор обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал.

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Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином автор обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал.

" } ["ORGANIZATION_RU"]=> array(37) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14202" ["VALUE"]=> array(2) { ["TEXT"]=> string(217) "<p>Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(205) "

Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

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Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

" } ["FULL_TEXT_RU"]=> array(37) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14205" ["VALUE"]=> array(2) { ["TEXT"]=> string(27448) "<h3>Уровень исследования</h3> <p class="bodytext"> На первый взгляд представляется очевидным, что при решении редколлегии соответствующего журнала в пользу или против публикации рукописи НС, самым существенным критерием ценности результатов является новизна. Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с <i>апоптозом</i> (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки. </p> <h3>Стиль</h3> <p class="bodytext"> Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями. </p> <h3>Заглавие</h3> <p class="bodytext"> Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков. </p> <h3>Введение </h3> <p class="bodytext"> Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность. </p> <h3>Материал и методика. Результаты</h3> <p class="bodytext"> В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка. </p> <h3>Обсуждение</h3> <p class="bodytext"> Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале. </p> <p class="bodytext"> Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе). </p> <h3>Перевод</h3> <p class="bodytext"> Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.<br> <br> •    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте <a href="http://www.senglish.narod.ru/books.html" target="_blank"><u>http://www.senglish.narod.ru/books.html</u></a><u>.</u> <br> <br> •    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности. <br> <br> •    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.<br> <br> •    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом. <br> <br> •    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала. </p> <h3>Литература</h3> <p class="bodytext"> 1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001. </p> <p class="bodytext"> 2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963. </p> <p class="bodytext"> 3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501. </p> <p class="bodytext"> 4. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0R-4M7CMHV-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a08a9319307df8c31ab91f8edb83231b" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004</u></a>. </p> <p class="bodytext"> 5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8. </p> <p class="bodytext"> 6. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSS-4183951-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5bbd5567c24ff8458d03ad14bd2c9ef8" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2</u></a>.  </p> <p class="bodytext"> 7. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33122/?tool=pubmed" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198</u></a>. </p> <p class="bodytext"> 8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр.  </p> <p class="bodytext"> 9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.<br> </p> <p class="bodytext"> 10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(26620) "

Уровень исследования

На первый взгляд представляется очевидным, что при решении редколлегии соответствующего журнала в пользу или против публикации рукописи НС, самым существенным критерием ценности результатов является новизна. Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с апоптозом (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки.

Стиль

Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями.

Заглавие

Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков.

Введение

Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность.

Материал и методика. Результаты

В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка.

Обсуждение

Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале.

Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе).

Перевод

Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.

•    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте http://www.senglish.narod.ru/books.html.

•    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности.

•    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.

•    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом.

•    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала.

Литература

1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр. 

9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.

10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999.

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Уровень исследования

На первый взгляд представляется очевидным, что при решении редколлегии соответствующего журнала в пользу или против публикации рукописи НС, самым существенным критерием ценности результатов является новизна. Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с апоптозом (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки.

Стиль

Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями.

Заглавие

Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков.

Введение

Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность.

Материал и методика. Результаты

В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка.

Обсуждение

Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале.

Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе).

Перевод

Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.

•    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте http://www.senglish.narod.ru/books.html.

•    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности.

•    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.

•    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом.

•    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала.

Литература

1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр. 

9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.

10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999.

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I read with much interest the article by Nevorotin providing advice to researchers from the states comprising the territories of the former Soviet Union who wish to have their work published in Western-based English language journals. I have served as a professional editor of journals focused on biomedical research for roughly 15 years now, first at Nature magazine and then at its sister journals, Nature Medicine and Nature Biotechnology. For the last eight years, I have served as the Editor of Molecular Therapy, which is the official journal of the American Society of Gene and Cell Therapy, and is published by Nature Group. During this time, I must admit that few submissions from this region passed over my desk. However, in my experience Nature Group and certainly Molecular Therapy have striven to be receptive to contributions of research articles from these regions and others in Asia, whose economies and research output are increasing rapidly in import.

Most editors realize the extra challenges faced by authors whose native language is not English. This issue is not limited to contributions from research labs physically located in the regions noted, but can also affect work submitted by post-docs hailing from these regions, but who now work in the West, particularly if the senior author does not proofread his or her penmanship. In my view, it is crucial that such authors pass their article to a biomedical researcher whose native language is English, but who is not directly involved in the work – or even in the specific subfield being written up. Why? Because a researcher more removed from the project can usually provide a better gage of the accessibility of its write-up for a general audience, assuming that the work is to be submitted to a high impact generalist journal, as opposed to a more subspecialty journal where the readers (and editors) are already likely familiar with much of the background and jargon of the particular field.

Indeed, it is this latter point that many authors – both native and non-native speakers of English – fail to appreciate. With the burgeoning volume of research articles, many editors find themselves overwhelmed by the sheer number of manuscripts they must screen. This initial editorial screen aims to determine whether the work merits external review or whether it should be returned to the author for submission elsewhere. This actually can be true both for professional editors at higher impact journals – who are no longer actively involved in bench or clinical science – and editors at society journals, who generally head up active research groups. Competition at high-impact journals is fierce. Acceptance rates can be as low at 10%. As such, the Editor must strive to select from myriad manuscripts landing on his or her desk those that fulfill the criteria of a potentially high-impact contribution. These criteria of course include novelty and scientific rigor and excellence, but must also include another important factor. The question an editor must try to answer is whether the work would be of interest to a broad spectrum of the readership; in other words, does the impact and general interest of the new findings extend beyond the narrow confines of the specific subfield of the research. This latter criteria is hard to gage, and is of course quite subjective. It is for this precise reason that the onus is on the author to emphasize in the clearest possible terms for both readers and most importantly the editor why the work is of general scientific interest and import. And remember, the editor is not reading this work in isolation, but rather from a pile of competing works that he or she is trying to whittle down within a limited period of time.

It is at this point that I cannot help but remember the reaction of my Ph.D. supervisor, McGill University researcher Nahum Sonenberg, to the first draft of my first manuscript authored under his guidance: “Keep it simple. People have too much to read already.” It is only over time I have realized how profound this seemingly simplistic advice actually was. For if you cannot explain very clearly and simply in few words the significance of your work, perhaps the work is in fact not that significant! Certainly, if you want to grab the attention of an editor or of those beyond your field, keeping the text and logical flow short, concise and simple can facilitate the appreciation of the work and its merits. I have always been somewhat obsessive-compulsive as I imagine are many who have gravitated to a scientific career – one gets focused on a specific problem, we want to understand it, and this can sometimes blind us to the greater context. In writing up our work, we aim to be precise and comprehensive, but this can often work against us, as we can lose many readers who may lack the same obsession and interest in our work!

Of course, most researchers based physically in the former East Bloc or Asia may not have easy access to a colleague willing to devote the time required to help with the write up of a research paper. In such cases, it may be useful to recruit the help of a professional scientific editing service. Such groups have been assisting researchers in Japan and other Asian countries for the past couple of decades. The services can range from simple correction of grammar, spelling and style to feedback on more substantive and developmental aspects of the write-up, and these can usually be negotiated directly with the service provider. I have worked with Nai, Inc., based in Yokohama since 2001, but there are a host of such services and NPG has recently got into the game with its own language editing service. I would be happy to steer any readers in the right direction in this regard.

Now, all the above notwithstanding, editors differ in their approach and style. This is why the most important thing an author can do is to engage the editor directly. This can be by discussing your work with an editor while at a conference or symposium or by simply emailing or calling the editor up. Send her or him an abstract to detemine whether the work fits the purview of the journal or would be of interest to the readership. Developing a relationship with the editor is probably the best thing an author can do to gain insight into the editorial process and standards at each particular journal and to get important feedback on one’s work and style of presentation. One thing that I have noted over the years is the variety of approaches and personalities amongst the incredibly idiosyncratic world of biomedical researchers. I have always been impressed by those who refuse to give up in the face of rejection and who persist in their dialogue with the editor, and who actively solicit feedback. A far more constructive approach than a terse email, verbal slight, or complete silence, none of which are likely to get an author anywhere!

The bottom line is that researchers from non-English speaking regions of the world face the same challenges as native speakers of a very competitive publishing environment, but with the added twist of having to learn the particular style and approach common to Western journals. The only way to learn to navigate through this environment is to simply jump in and take a few hits, for it really is only through experience and trial and error that an author can learn what works for him or her.

" ["~DETAIL_TEXT"]=> string(7530) "

I read with much interest the article by Nevorotin providing advice to researchers from the states comprising the territories of the former Soviet Union who wish to have their work published in Western-based English language journals. I have served as a professional editor of journals focused on biomedical research for roughly 15 years now, first at Nature magazine and then at its sister journals, Nature Medicine and Nature Biotechnology. For the last eight years, I have served as the Editor of Molecular Therapy, which is the official journal of the American Society of Gene and Cell Therapy, and is published by Nature Group. During this time, I must admit that few submissions from this region passed over my desk. However, in my experience Nature Group and certainly Molecular Therapy have striven to be receptive to contributions of research articles from these regions and others in Asia, whose economies and research output are increasing rapidly in import.

Most editors realize the extra challenges faced by authors whose native language is not English. This issue is not limited to contributions from research labs physically located in the regions noted, but can also affect work submitted by post-docs hailing from these regions, but who now work in the West, particularly if the senior author does not proofread his or her penmanship. In my view, it is crucial that such authors pass their article to a biomedical researcher whose native language is English, but who is not directly involved in the work – or even in the specific subfield being written up. Why? Because a researcher more removed from the project can usually provide a better gage of the accessibility of its write-up for a general audience, assuming that the work is to be submitted to a high impact generalist journal, as opposed to a more subspecialty journal where the readers (and editors) are already likely familiar with much of the background and jargon of the particular field.

Indeed, it is this latter point that many authors – both native and non-native speakers of English – fail to appreciate. With the burgeoning volume of research articles, many editors find themselves overwhelmed by the sheer number of manuscripts they must screen. This initial editorial screen aims to determine whether the work merits external review or whether it should be returned to the author for submission elsewhere. This actually can be true both for professional editors at higher impact journals – who are no longer actively involved in bench or clinical science – and editors at society journals, who generally head up active research groups. Competition at high-impact journals is fierce. Acceptance rates can be as low at 10%. As such, the Editor must strive to select from myriad manuscripts landing on his or her desk those that fulfill the criteria of a potentially high-impact contribution. These criteria of course include novelty and scientific rigor and excellence, but must also include another important factor. The question an editor must try to answer is whether the work would be of interest to a broad spectrum of the readership; in other words, does the impact and general interest of the new findings extend beyond the narrow confines of the specific subfield of the research. This latter criteria is hard to gage, and is of course quite subjective. It is for this precise reason that the onus is on the author to emphasize in the clearest possible terms for both readers and most importantly the editor why the work is of general scientific interest and import. And remember, the editor is not reading this work in isolation, but rather from a pile of competing works that he or she is trying to whittle down within a limited period of time.

It is at this point that I cannot help but remember the reaction of my Ph.D. supervisor, McGill University researcher Nahum Sonenberg, to the first draft of my first manuscript authored under his guidance: “Keep it simple. People have too much to read already.” It is only over time I have realized how profound this seemingly simplistic advice actually was. For if you cannot explain very clearly and simply in few words the significance of your work, perhaps the work is in fact not that significant! Certainly, if you want to grab the attention of an editor or of those beyond your field, keeping the text and logical flow short, concise and simple can facilitate the appreciation of the work and its merits. I have always been somewhat obsessive-compulsive as I imagine are many who have gravitated to a scientific career – one gets focused on a specific problem, we want to understand it, and this can sometimes blind us to the greater context. In writing up our work, we aim to be precise and comprehensive, but this can often work against us, as we can lose many readers who may lack the same obsession and interest in our work!

Of course, most researchers based physically in the former East Bloc or Asia may not have easy access to a colleague willing to devote the time required to help with the write up of a research paper. In such cases, it may be useful to recruit the help of a professional scientific editing service. Such groups have been assisting researchers in Japan and other Asian countries for the past couple of decades. The services can range from simple correction of grammar, spelling and style to feedback on more substantive and developmental aspects of the write-up, and these can usually be negotiated directly with the service provider. I have worked with Nai, Inc., based in Yokohama since 2001, but there are a host of such services and NPG has recently got into the game with its own language editing service. I would be happy to steer any readers in the right direction in this regard.

Now, all the above notwithstanding, editors differ in their approach and style. This is why the most important thing an author can do is to engage the editor directly. This can be by discussing your work with an editor while at a conference or symposium or by simply emailing or calling the editor up. Send her or him an abstract to detemine whether the work fits the purview of the journal or would be of interest to the readership. Developing a relationship with the editor is probably the best thing an author can do to gain insight into the editorial process and standards at each particular journal and to get important feedback on one’s work and style of presentation. One thing that I have noted over the years is the variety of approaches and personalities amongst the incredibly idiosyncratic world of biomedical researchers. I have always been impressed by those who refuse to give up in the face of rejection and who persist in their dialogue with the editor, and who actively solicit feedback. A far more constructive approach than a terse email, verbal slight, or complete silence, none of which are likely to get an author anywhere!

The bottom line is that researchers from non-English speaking regions of the world face the same challenges as native speakers of a very competitive publishing environment, but with the added twist of having to learn the particular style and approach common to Western journals. The only way to learn to navigate through this environment is to simply jump in and take a few hits, for it really is only through experience and trial and error that an author can learn what works for him or her.

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array(2) { ["TEXT"]=> string(56) "<p>Роберт М. Фредриксон</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(44) "

Роберт М. Фредриксон

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Редактор журнала "Molecular Therapy", www.nature.com/mt

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Комментарий к статье Алексея И. Неворотина "Научные статьи на английском языке: что следует учитывать перед отправкой рукописи"

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Robert M. Frederickson

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Editor Molecular Therapy, www.nature.com/mt

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Commentary on Alexander Nevorotin, Research articles in English: what should be considered before submitting a manuscript

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14228" ["VALUE"]=> string(58) "Scientific writing navigation: jump in and take a few hits" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(58) "Scientific writing navigation: jump in and take a few hits" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14229" ["VALUE"]=> array(2) { ["TEXT"]=> string(14955) "<p class="bodytext"> Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале <i>Nature</i>, а потом – в изданиях той же группы - <i>Nature Medicine</i> и <i>Nature Biotechnology</i>. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается <i>Nature Group</i>. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований. <br>   <br> Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.<br> <br> Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени. <br> <br> Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе! <br> <br> Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией <i>Nai, Inc.</i>, находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг <i>NPG</i> также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении. <br> <br> Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору!  <br> <br> В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(14789) "

Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале Nature, а потом – в изданиях той же группы - Nature Medicine и Nature Biotechnology. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается Nature Group. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований.
 
Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.

Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени.

Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе!

Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией Nai, Inc., находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг NPG также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении.

Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору! 

В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу.

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Frederickson" ["LINK_ELEMENT_VALUE"]=> bool(false) } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14232" ["VALUE"]=> array(2) { ["TEXT"]=> string(492) "<p class="bodytext"> <b>Комментарий к статье <a href="http://www.cttjournal.com/ru/archive/tom-1-nomer-4/forum/nauchnaya-statya-na-angliyskom-yazyke-o-chem-stoit-podumat-pered-otpravkoy-rukopisi/">Алексея И. Неворотина "Научные статьи на английском языке: что следует учитывать перед отправкой рукописи"</a></b> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(426) "

Комментарий к статье Алексея И. Неворотина "Научные статьи на английском языке: что следует учитывать перед отправкой рукописи"

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Комментарий к статье Алексея И. Неворотина "Научные статьи на английском языке: что следует учитывать перед отправкой рукописи"

" } ["ORGANIZATION_RU"]=> array(37) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14226" ["VALUE"]=> array(2) { ["TEXT"]=> string(237) "<p class="bodytext"> Редактор журнала "Molecular Therapy", <a href="http://www.nature.com/mt" target="_blank"><u>www.nature.com/mt</u></a> </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(161) "

Редактор журнала "Molecular Therapy", www.nature.com/mt

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["DISPLAY_VALUE"]=> string(161) "

Редактор журнала "Molecular Therapy", www.nature.com/mt

" } ["FULL_TEXT_RU"]=> array(37) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "14229" ["VALUE"]=> array(2) { ["TEXT"]=> string(14955) "<p class="bodytext"> Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале <i>Nature</i>, а потом – в изданиях той же группы - <i>Nature Medicine</i> и <i>Nature Biotechnology</i>. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается <i>Nature Group</i>. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований. <br>   <br> Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.<br> <br> Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени. <br> <br> Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе! <br> <br> Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией <i>Nai, Inc.</i>, находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг <i>NPG</i> также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении. <br> <br> Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору!  <br> <br> В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу. </p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(14789) "

Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале Nature, а потом – в изданиях той же группы - Nature Medicine и Nature Biotechnology. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается Nature Group. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований.
 
Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.

Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени.

Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе!

Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией Nai, Inc., находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг NPG также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении.

Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору! 

В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу.

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Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале Nature, а потом – в изданиях той же группы - Nature Medicine и Nature Biotechnology. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается Nature Group. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований.
 
Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.

Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени.

Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе!

Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией Nai, Inc., находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг NPG также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении.

Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору! 

В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу.

" } } } }
Volume 1, Number 4
03/01/2010
Volume 1, Number 4
Editor-in-Chief
Afanasyev B. V. (St. Petersburg, Russia)
Co-Editors-in-Chief
Wagemaker G. (Rotterdam, Netherlands)
Zander A. R. (Hamburg, Germany)
Deputy Editor
Chukhlovin A. B. (St. Petersburg, Russia)
Fehse B. (Hamburg, Germany)
Novik A. А. (Moscow, Russia)
Managing Editor
Claudia Koltzenburg (Hamburg, Germany)
Editorial Board
Aleynikova O. (Minsk, Belarus)
Alyansky A. (St. Petersburg, Russia)
Anagnostou A. (Boston, USA)
Andreeff M. (Houston, USA)
Bacher U. (Hamburg, Germany)
Baуkov V. (St. Petersburg, Russia)
Baranov V. S. (St. Petersburg, Russia)
Barkhatov I. (St. Petersburg, Russia)
Baum C. (Hannover, Germany)
Bilko N. (Kiev, Ukraine)
Borset M. (Trondheim, Norway)
Buechner Th. (Muenster, Germany)
Bykov V. (St. Petersburg, Russia)
Dini G. (Genoa, Italy)
Drize N. (Moscow, Russia)
Egeland T. (Oslo, Norway)
Elstner E. (Berlin, Germany)
Emanuel V. (St. Petersburg, Russia)
Everaus H. (Tartu, Estonia)
Ferrara J. (Ann Arbor, USA)
Fibbe W. (Leiden, Netherlands)
Galibin O. (St. Petersburg, Russia)
Ganser A. (Hannover, Germany)
Granov D. (St. Petersburg, Russia)
Ivanov R. (Moscow, Russia)
Klimko N. (St. Petersburg, Russia)
Kolb H.-J. (Muenchen, Germany)
Konopleva M. (Houston, USA)
Koza V. (Pilsen, Czech Republic)
Kroeger N. (Hamburg, Germany)
Malikov A. (St. Petersburg, Russia)
Mikhailova N. (St. Petersburg, Russia)
Mentkevich G. (Moscow, Russia)
Nagler A. (Tel Hashomer, Israel)
Nemkov A. (St. Petersburg, Russia)
Neth R. (Hamburg, Germany)
Nevorotin A.J. (St. Petersburg, Russia)
Ostertag W. (Hamburg, Germany)
Palutke M. (Detroit, USA)
Roumiantsev A. G. (Moscow, Russia)
Savchenko V. G. (Moscow, Russia)
Smirnov A. V. (St. Petersburg, Russia)
Stamm C. (Berlin, Germany)
Tetz V. (St. Petersburg, Russia)
To B. (Adelaide, Australia)
Totolian A. A. (St. Petersburg, Russia)
Uss A.L. (Minsk, Belarus)
Vilesov A. (St. Petersburg, Russia)
Westenfelder Ch. (Salt Lake City, USA)
Wisloff F. (Oslo, Norway)
Zubarovskaya L. (St. Petersburg, Russia)
Zvartau E. (St. Petersburg, Russia)
In this Issue

When we were asked to edit a special issue of Cellular Therapy and Transplantation (CTT) on the topic of Gene and Cell Therapy, it was quite clear that this would be a demanding task. As is well known, there are a number of excellent, high-ranked journals representing (or cooperating with) the leading international and national societies established in this research area. For a newcomer journal this means tough competition to get some manuscripts of significant impact.

Despite its relatively short history, CTT has already established a nice tradition which made life much easier. The journal tries to devote some space to historical, ground-breaking work. It wasn’t too difficult to identify a publication cited in multiple gene therapy reviews, but hardly read by any of the younger researchers due to accessibility problems. In fact, the manuscript by Edward Tatum based on a lecture he gave in May 1966 contains a very concrete and elaborate vision of the possibilities offered by a novel technique which he named genetic therapy. The visionary power of Tatum’s article is really astonishing; particularly if one considers that he wrote his article at a time when the techniques of recombinant DNA were still to be invented. As good Science fiction Tatum’s article is still, more than 40 years after its publication, very enjoyable, even if one does not agree with all his ideas. We suggest that going back to the roots will be interesting for everybody working in the field.

We are also happy that Charles Coutelle from Imperial College London, a pioneer in basic and translational gene therapy research, agreed to write a Commentary on Tatum’s article. This commentary is much more than reminiscence; analyzing Tatum’s work from the today’s point of view Charles raises a number of important and critical issues to be resolved in modern genetics and gene therapy.

The present issue contains two very interesting articles on regulatory issues in gene and cell therapy, one by Christine Voelkel and colleagues devoted to retrovirus-mediated gene transfer into hematopoietic stem cells, and the other by Anja Elstner et al. on the regulatory landscape in human ES cell research. We are certain that these contributions will be of interest for many readers active or interested in clinical gene therapy and ES stem cell research.

We are pleased to present the work by Vera V. Sergeevicheva and colleagues on a clinical study with mesenchymal stromal cells in Novosibirsk, Russia. The authors found improved hematopoietic recovery in MSC-treated hemoblastosis (proliferative disorders of blood-forming cells) patients after hematopoietic stem cell transplantation. This publication also underlines the journal’s policy to provide space for important contributions from Eastern countries.

The introduction of novel ways of publishing is another main focus of CTT. In line with this, this issue contains a video publication on the in vitro behavior of MSC. The contribution by Claudia Lange and colleagues clearly illustrates the advantages associated with the novel possibilities of data presentation offered by the internet.

Sooner or later many researchers working with last-generation Becton Dickinson flow cytometers experience that with regard to data presentation and figure export, FACS-Diva software clearly represents a pain point of these high-end devices. In their Method paper, Kristoffer Weber and Boris Fehse introduce their straightforward and easy method to overcome these limitations, step-by-step.

Diagnostics and therapy of Philadelphia chromosome-positive leukemia have been revolutionized in the last decade. This was a stimulus for the journal to devote this issue’s state-of-the art Hematology review to these topics. We are happy that Nikolay N. Mamaev accepted the Editor’s invitation and provided a very comprehensive overview on Ph+ leukemia.

Finally, we use the current issue of CTT to introduce a novel format in the journal, namely a Forum for the discussion of topics of interest for the scientific community. The first contribution to the Forum section comes from Alexey I. Nevorotin who, based on his own extensive experience, provides writing advice for Russian scientists who want to publish their results in English-language journals. We are very grateful that Robert M. Frederickson, one of the most experienced editors in the field, currently Editor of Molecular Therapy, one of the top journals in experimental medicine, agreed to contribute his personal view on this topic in a comprehensive article also published in the Forum section of this issue.

Besides the contributors we have to thank the colleagues who made this issue possible. Firstly, thanks to the managing editor Claudia Koltzenburg and her team (René J. Hornung, Liudmila Lashkouskaya, Melissa Pritchard, and Anna Starikova) who have done a great job.

Following another nice tradition of the journal we are delighted to thank the reviewers of this issue for their invaluable help: Ulrike Bacher, Alexey B. Chukhlovin, Ulrike Köhl, Srinivas Koduru, Claudia Lange, Binghua Li, Vladimir Prassolov, Axel Schambach, Bernd Schiedlmeier, Sonja Schrepfer, Alexander B. Smolyaninov, Anna G. Turkina, and Anke Wahlers. Also, we have to thank The Johns Hopkins University Press for the opportunity to obtain a reprint licence of the Tatum article. Last but not least, we are indebted to the Deutsche Forschungsgemeinschaft for supporting this open access journal project.

Boris Fehse, Christopher Baum

Keynote

Keynote comment

Articles

Ongoing dynamics in the regulatory landscape of human embryonic stem cell research

Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

* Both authors contributed equally

Retrovirus mediated hematopoietic gene therapy: A European regulatory perspective with special focus on the situation in Germany

Christine Voelkel1,2, Anke Lührmann2, Christopher Baum1,3, and Heiko E. von der Leyen2

Autologous mesenchymal stromal cells of hemoblastosis patients efficiently support hematopoietic recovery after stem cell transplantation

Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

The MSCs' in vitro community: where to go?

Sascha Lange, Axel R. Zander, Claudia Lange

Methods

Hematology review

Forum

Keynote

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Э. Л. Тэйтум

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Molecular biology, nucleic acids, and the future of medicine.

Reprinted with Permission of The Johns Hopkins University Press.
Originally published in: Perspectives in Biology and Medicine 10:1 (1966), 19-32.

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E. L. Tatum

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Rockefeller University, New York, New York

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Reprinted with Permission of The Johns Hopkins University Press.
Originally published in: Perspectives in Biology and Medicine 10:1 (1966), 19-32.

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Molecular biology, nucleic acids, and the future of medicine

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E. L. Tatum

Rockefeller University, New York, New York

Reprinted with Permission of The Johns Hopkins University Press.
Originally published in: Perspectives in Biology and Medicine 10:1 (1966), 19-32.

Keynote comment

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Charles Coutelle

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Emeritus Professor of Gene Therapy, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Molecular and Cellular Medicine Section, SW7 2AZ UK

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Edward Lewis Tatum’s vision of the future of medicine. [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => From mould to man. Edward Lewis Tatum’s vision of the future of medicine. [~DESCRIPTION] => [~NAME] => Name [~DEFAULT_VALUE] => ) [FULL_TEXT_RU] => Array ( [ID] => 42 [TIMESTAMP_X] => 2015-09-07 20:29:18 [IBLOCK_ID] => 2 [NAME] => Полный текст [ACTIVE] => Y [SORT] => 500 [CODE] => FULL_TEXT_RU [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 42 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13422 [VALUE] => Array ( [TEXT] => <p class="bodytext">«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)<br /><br />Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.<br /><br />Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.<br /><br />Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо. </p> <p class="bodytext">Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями. </p> <p class="bodytext">Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения. </p> <p class="bodytext">С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой. </p> <p class="bodytext">Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее. </p> <p class="bodytext">Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах. </p> <p class="bodytext">Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума. </p> <p class="bodytext">Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

«Если я и видел дальше, то потому, что стоял на плечах гигантов» (Сэр Исаак Ньютон)

Более 40 лет тому назад, точнее – в мае 1966 года, Эдвард Тэйтум, столетие со дня рождения которого будет отмечаться в декабре этого года, выступил с провидческой речью о будущем медицины.  Тэйтум был одним из отцов-основателей заново возникшей области науки – молекулярной биологии. В 1958 г. он получил Нобелевскую премию по медицине за свои работы 1930-40х гг. совместно с Джорджем Бидлом по радиационно-индуцированным изменениям грибка Neurospora crassa. Они показали, что гены контролируют метаболические процессы, определяя функции конкретных ферментов. Это открытие привело к появлению гипотезы «один ген – один энзим».  Двуспиральная структура ДНК была открыта лишь за 5 лет до этого, и, кроме того, в 1958 году Крик сформулировал центральную догму молекулярной биологии, где все было сведено воедино.

Тэйтум, вероятно, мыслил с тех пор о влиянии, которое эти новые биологические концепции могут оказать на здоровье и благополучие человека. С настоятельным предупреждением о том, что предсказание будущего не является его занятием, он в своем выступлении стремится предсказать, в какой мере эти открытия могли бы изменить медицину в последующие 10 или 20 лет.  Для нас, имеющих выгодную возможность оглянуться назад, удивительно видеть результат этих предсказаний. За исключением иммунологии и неврологии, о которых шла речь в других выступлениях на той же встрече, Тэйтум был весьма точен в предсказании общих направлений, по которым новые знания поведут  медицинскую науку, а также в описании тех терапевтических целей, к достижению которых будет стремиться  медицина.  Другие предсказания менее точны, в основном, в отношении сроков исполнения и сложности задач.

Однако, настоятельное предупреждение Тэйтума в начале его выступления о росте мирового населения и ограниченности естественных ресурсов не было последовано. На основании современных знаний мы могли бы также добавить к этим угрозам и климатические изменения. Даже если ужасные последствия, прогнозируемые им, еще не достигли полного развития, то мы уже видим их появление.  К сожалению, реакции политиков, такие, как военные авантюры для обеспечения безопасности ресурсов, неудачи политических усилий, не направленные, в первую очередь, на создание стабильных и конкурентоспособных экономик в развивающемся мире и отсутствие решений, или даже прямое отрицание климатических изменений, являются в большой мере неадекватными ответами на эти вызовы. Эти предостережения сегодня являются даже более актуальными, чем что-либо другое, и изменения в политических подходах для того, чтобы справиться с этими  проблемами, нужны еще в большей мере, чем когда-либо.

Согласно его предсказаниям, молекулярная вирусология привела к огромному прорыву в понимание биологии многих вирусов и, как следствие этого, – к  разработке новых и эффективных стратегий борьбы с вирусными болезнями.  Однако мы все еще далеки  от победы над  «почти всеми» вирусными заболеваниями.

Высокая  изменчивость ряда вирусов, позволяющая им избегать исходно эффективной терапии, не могла быть им предсказана.  Еще менее предсказуемым оказалось появление новых вирусных болезней, вызываемых ВИЧ, вирусом Эбола, SARS.  Некоторые из них возникли из патогенных вирусов животных. Урок, который предстоит усвоить, состоит в том, что  взаимодействия в системе «вирус-человек» являются частью нашей генетической организации и эволюционного наследия и, вероятно, всегда будут оставаться важными для человечества. Несомненно, что будут возникать новые проблемы, однако постоянный рост  знаний в области биологии будет повышать наши возможности в борьбе с вирусными заболеваниями путем профилактики и эффективного лечения.

С другой стороны, вирусы  стали важным инструментом исследования и, как предвидел Тэйтум, они могут быть использованы для внесения терапевтической ДНК в дефектные клетки-мишени. Задолго до создания методов культивирования и  клеток человека, он предположил протокол генной терапии гепатоцитов ex vivo. На выступление Тейтума часто ссылаются как на одно из первых предсказаний возможности генной терапии человека. Однако  потребовалось время до начала 90-х годов, когда были проведены первые клинические испытания, и еще почти 10 лет после этого до первого успешного опыта лечения в 1999 г больных с тяжелым комбинированным иммунодефицитом, сцепленным с Х-хромосомой.

Аналогично, не отрицая большие успехи в исследовании и лечении рака, что подтверждает общее направление предсказаний Тэйтума, прогноз познания основных причин рака в пределах указанных им сроков кажется чересчур оптимистичным, несмотря на признание большой сложности этой группы заболеваний. Возникновение клеточной биологии, которая объединяет открытия молекулярной биологии на уровне клетки -  мельчайшей единицы живого – является одним из достижений биомедицинской науки для достижения желаемых целей в познании рака и других заболеваний. И в самом деле, сегодня, спустя примерно 40 лет,  знания молекулярной и клеточной биологии, иммунологии и молекулярной фармакологии, включая генную терапию, объединенные в базовый научный арсенал молекулярной медицины, начинают обеспечивать первые эффективные профилактические мероприятия и исцеляющее лечение, которые предсказывались ранее.

Несмотря на знания о генных мутациях как молекулярной основе генетических заболеваний, понадобилось около 20 лет для того, чтобы разработать стратегию выявления отдельных генов и мутаций, ответственных за большинство этих заболеваний, при которых фенотип не всегда указывает на то, какой именно  белок является дефектным. Эта стратегия «обратной генетики» или «позиционного клонирования» была впервые использована при  анализе хронического грануломатоза и миодистрофии Дюшенна в 1986 году, затем в 1989 г. – при изучении кистофиброза и в 1990 г. – нейрофиброматоза I типа. Эти поиски генов потребовали совместных усилий ученых разных стран на протяжении более 10 лет. В настоящее время, на основе результатов завершенного проекта «Геном Человека» и набора маркеров, перекрывающих весь геном, такой поиск генов может быть осуществлен в течение месяцев или даже недель. Эти огромные шаги вперед стали возможными только благодаря предшествующему развитию методов работы с рекомбинантными ДНК in vitro и технологий молекулярного клонирования в середине 70-х и 80-х годах.

Идеи Тэйтума о применении знаний молекулярной биологии для выявления у носителей генных мутаций, которые приводят к развитию болезней, были реализованы в начале 80-х годов в отношении многих моногенных болезней. Тэйтум, несомненно, был вдохновлен глубоко гуманистической ответственностью, стремясь к цели «улучшения жизни, наследственности и здоровья человека». Однако, социальная концепция  «евгенической инженерии» состоящая в том , чтобы сделать «скромную попытку снизить частоту и экспрессию нежелательных генов» путем «более важного … общего восприятия индивидами их социальной ответственности с тем, чтобы не передавать эти гены по наследству» не может  быть не оспорена. Речь тут не только идёт о неудачном использовании исторически скомпрометированного выражения «евгеника». Идея общественного или морального давления с целью повлиять на индивидуальные решения в плане репродукции, ради предполагаемого «большего блага человечества»  в весьма отдаленном будущем, не может быть принята безоговорочно. Мы уже видим, что  определение последовательности генома индивидуумов может дать информацию о множестве нежелательных генетических признаков. Вероятно, у каждого человека можно показать наличие одного или нескольких таких генов. Поскольку в настоящее время все шире принимается принцип «хорошей практики» в ДНК-диагностике, то надо уделять большое внимание тому, чтобы обрабатывать эти данные конфиденциально, и чтобы избегать в ходе профессионального генетического консультирования излишней демонстрации и ненужного беспокойства, а также дать возможность обследуемому лицу принять информированные решения по вопросам репродукции и/или образу жизни, в соответствии с его персональным выбором. Такие индивидуальные решения, конечно, могут в большой мере зависеть  от перспектив эффективного или даже исцеляющего лечения и успехов репродуктивной медицины. Дальнейшее совершенствование в этих областях медицины находится в пределах нашей ответственности, во исполнение гуманистических заветов Тэйтума.

Эдвард Льюис Тэйтум был одним из научных гигантов, на плечах которых мы стоим в ходе дальнейшего развития молекулярной биологии и ее применения во имя здоровья и благополучия человека. Успехи медицины за последние 40 лет, как он и предсказывал, предлагали ранее и предлагают теперь новые решения, в том числе генную терапию. Даже его взгляды на лечение генетического заболевания путем коррекции мутации кажется нам теперь выполнимой целью. Если она будет достижима и безопасна для будущих поколений, то надо решить, может ли быть разработан подход к коррекции нежелательных генных последовательностей на уровне зародышевых клеток, обоснованный с точки зрения медицины и приемлемый с позиций этики.

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From mould to man. Edward Lewis Tatum’s vision of the future of medicine.

Download PDF version

Charles Coutelle

Emeritus Professor of Gene Therapy, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Molecular and Cellular Medicine Section, SW7 2AZ UK

Articles

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Аня Эльстнер*, Аннетт Ноак*, Александр Дамашун, Глин Стэйси, Бегонья Аран, Илона Гавронска, Анна Вейга,
Йори Борстлап, Андреас Куртц

* Вклад обоих авторов одинаков

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Авторы [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [ORGANIZATION_RU] => Array ( [ID] => 26 [TIMESTAMP_X] => 2015-09-02 18:01:20 [IBLOCK_ID] => 2 [NAME] => Организации [ACTIVE] => Y [SORT] => 500 [CODE] => ORGANIZATION_RU [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 26 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => [VALUE] => [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => [~DESCRIPTION] => [~NAME] => Организации [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_RU] => Array ( [ID] => 27 [TIMESTAMP_X] => 2015-09-02 18:01:20 [IBLOCK_ID] => 2 [NAME] => Описание/Резюме [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_RU [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 27 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13651 [VALUE] => Array ( [TEXT] => <p class="bodytext">Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, <a href="http://www.hescreg.eu/" target="_blank">www.hescreg.eu</a>), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.</p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Специфика межнациональных особенностей основ правового регулирования в области научных исследований эмбриональных стволовых клеток человека (ЭСКЧ) все еще остается весьма сложным вопросом из-за множества исторических, культурных и этических мнений, которые преобладают в тех или иных странах. Путем учреждения Европейского Регистра стволовых клеток человека (ЕРСК, hESCreg, www.hescreg.eu), Европейский Союз в 2007 г. инициировал первую концепцию, касающуюся сравнений и научно обоснованной гармонизации законодательства в области ЭСКЧ. Консорциум ЕРСК в настоящее время включает в себя представителей 15 стран (в том числе европейских и неевропейских государств), которые действуют в качестве национальных контактных организаций, и регулярно обновляют Регистр информацией о стволовых клетках, а также о законодательных и этических дискуссиях в области исследований стволовых клеток. Некоторые из этих стран недавно испытали серьезные изменения законодательства, которые вступили в силу в Китае, Финляндии, Норвегии, Великобритании и США. В других странах ожидаются изменения правил в близком будущем, как, например, в Австралии, Индии и Турции. В то время как многие страны ввели законоположения, направленные на либерализацию исследований ЭСК, некоторые государства придерживаются более строгих правил, касающихся ЭСК (например, Турция, Германия. Венгрия и Италия). В данной статье обобщена и собрана информация о нынешнем состоянии международных правил ЕРСК, которая представлена нами в настоящем докладе.

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Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

* Both authors contributed equally

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1Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Germany; 2The UK Stem Cell Bank, National Institute for Biological Standards and Control, South Mimms, UK; 3Banc de Linies Cel.lulars, Center of Regenerative Medicine Barcelona (CMRB); 4Institut Universitari Dexeus, Barcelona, Spain

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Organization [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_EN] => Array ( [ID] => 39 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Description / Summary [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 39 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13667 [VALUE] => Array ( [TEXT] => <p class="bodytext">The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.</p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.

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Ongoing dynamics in the regulatory landscape of human embryonic stem cell research

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Anja Elstner*1, Annette Noack*1, Alexander Damaschun1, Glyn Stacey2, Begoňa Arán3, Ilona Gawronska1, Anna Veiga3,4,
Joeri Borstlap1 and Andreas Kurtz1

* Both authors contributed equally

1Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Germany; 2The UK Stem Cell Bank, National Institute for Biological Standards and Control, South Mimms, UK; 3Banc de Linies Cel.lulars, Center of Regenerative Medicine Barcelona (CMRB); 4Institut Universitari Dexeus, Barcelona, Spain

The international situation regarding the specific nature of regulation on human embryonic stem cell research is still quite complex due to pluralistic historical, cultural and ethical opinions that dominate in respective countries. By establishing the Human European Stem Cell Registry (hESCreg, www.hescreg.eu) in 2007, the EU initiated the first steps towards comparison and science-driven harmonization of hESC legislation. The hESCreg consortium currently includes representatives from 15 countries (including European and non-European countries), who act as National Contacts for hESCreg and regularly update the registry with information on stem cells as well as legislative and ethical discussions in the field of stem cell research. Several of these countries have experienced recent legislative changes; these were implemented in China, Finland, the Netherlands, Norway, the United Kingdom, and the USA. Others expect regulatory changes in the near future, such as in Australia, India, and Turkey. Whilst many countries have introduced legislation to liberalize embryonic stem cell research, others hold to stricter regulations on embryo-derived stem cells (e.g. Turkey, Germany, Hungary, and Italy). In this article we summarize and complete the information on the current status of international hESC regulation provided in our recent report.

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Велькель К., Люрманн А., Баум К., фон дер Ляйен Х.Э.

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Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта. <br /><br />Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов. <br /><br />Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. <br /><br />Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Генная терапия предназначена для лечения генетических дефектов путем введения корригированной копии мутантного гена. Однако, в отличие от классического лекарственного лечения, генная терапия является подходом, высокоспецифичным в отношении больного и заболевания. Трансген как таковой должен быть адаптирован к каждому специфическому подходу и медицинской цели. С 1989 по 2009 гг. были одобрены  1537 клинических испытаний в области генной терапии с применением 35 различных типов векторов. Кроме того, с одной стороны, генно-терапевтический подход позволяет достичь эффективной долгосрочной коррекции генетического дефекта, а с другой стороны – несет опасность побочных эффектов. Ряд работ по лечению тяжелого комбинированного иммунодефицита, сцепленного с Х-хромосомой, показал развитие у нескольких больных лимфопролиферативных заболеваний в связи с инсерционным мутагенезом. Такие побочные эффекты, наряду с иммуногенностью, передачей генетических последовательностей, а также токсичных и инфекционных побочных продуктов, связанных с приготовлением вектора, делает необходимой строгое регулирование их применения со стороны властей. Соответствующие правила могут быть определены лишь в общих понятиях, и нельзя создать единый документ, пригодный для конкретной цели и индивидуального использования каждого продукта.

Встраивающиеся векторы, дефектные по репликационным свойствам, основанные на гамма-ретровирусах, часто применялись в исходных протоколах генной терапии, и их опасность может обсуждаться в качестве примера, в частности, инсерционный мутагенез, который возникает во многом из-за случайного характера встраивания  вируса по отношению к целевым генным локусам. Кроме того, могут быть вызваны и генотоксические эффекты, в основном связанные с дизрегуляцией активности нормальных генов при введении регуляторных элементов в составе вектора. Другой крупной проблемой вирусного переноса генов является их «вертикальный» перенос в зародышевых клеточных линиях, в частности, через пролиферирующие сперматогониальные клетки, которые могут быть мишенью для гамма-ретровирусных векторов.

Для того, чтобы упредить эти опасности, регулирующая система должна уточнить единообразные требования для того, чтобы обеспечить соответствия между стандартами качества и, тем самым, гарантировать безопасность участников испытания. Данная статья суммирует наиболее важные регулирующие документы, которые следует учитывать до вхождения в фазу клинической разработки – не только для Германии, но и в европейской перспективе. Приводятся ссылки на применимые для этого руководящие указания в отношении генно-терапевтических медицинских продуктов (ГТМП), с соответствующими определениями для таких продуктов. 

Производство ГТМП должно согласовываться с требованиями Директивы Европейского Союза 2003/94/EC о качественной практике производства  (GMP). В Германии эта практика регулируется Предписаниями по производству медицинских продуктов и активных фармацевтических ингредиентов (AMWHV). Важно, чтобы особые аспекты безопасности в отношении ГТМП учитывались до использования этих продуктов в клинике. В любом случае, регулирующие указания имеют в своей основе: (1) имеющиеся научные знания, (2) научный опыт в данной области исследований, и они  возникают в результате постоянного взаимодействия между исследователями и экспертами в области регулирования.

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Описание/Резюме [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [DOI] => Array ( [ID] => 28 [TIMESTAMP_X] => 2016-04-06 14:11:12 [IBLOCK_ID] => 2 [NAME] => DOI [ACTIVE] => Y [SORT] => 500 [CODE] => DOI [DEFAULT_VALUE] => [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 80 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 28 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => [USER_TYPE_SETTINGS] => [HINT] => [PROPERTY_VALUE_ID] => 13452 [VALUE] => 10.3205/ctt-2009-en-000044.01 [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => 10.3205/ctt-2009-en-000044.01 [~DESCRIPTION] => [~NAME] => DOI [~DEFAULT_VALUE] => ) [AUTHOR_EN] => Array ( [ID] => 37 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Author [ACTIVE] => Y [SORT] => 500 [CODE] => AUTHOR_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 37 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13502 [VALUE] => Array ( [TEXT] => <p> Christine Voelkel<sup>1,2</sup>, Anke Lührmann<sup>2</sup>, Christopher Baum<sup>1,3</sup>, and Heiko E. von der Leyen<sup>2</sup> </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Christine Voelkel1,2, Anke Lührmann2, Christopher Baum1,3, and Heiko E. von der Leyen2

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Author [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [ORGANIZATION_EN] => Array ( [ID] => 38 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Organization [ACTIVE] => Y [SORT] => 500 [CODE] => ORGANIZATION_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 38 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13503 [VALUE] => Array ( [TEXT] => <p class="bodytext"><sup>1</sup>Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;<br><sup> 2</sup>Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany; <br><sup>3</sup>Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA </p> <br> <p> <b>Correspondence </b><br>Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany, <br>Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.zhpicirDgpmrmgep1xvmep1girxiv2hi');">vdleyen@<span style="display:none;">spam is bad</span>clinical-trial-center.de</a> </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

1Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;
2Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany;
3Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA


Correspondence
Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany,
Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: vdleyen@spam is badclinical-trial-center.de

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Retrovirus mediated hematopoietic gene therapy: A European regulatory perspective with special focus on the situation in Germany

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Christine Voelkel1,2, Anke Lührmann2, Christopher Baum1,3, and Heiko E. von der Leyen2

1Department of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany;
2Hannover Clinical Trial Center GmbH, D-30625 Hannover, Germany;
3Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA


Correspondence
Prof. Dr. Heiko E. von der Leyen, Hannover Clinical Trial Center GmbH, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany,
Tel.: +49 511 533 333 0, Fax: +49 511 533 333 99, E-mail: vdleyen@spam is badclinical-trial-center.de

Retrovirus mediated gene therapy has already proven to be more than just a theoretical option to treat patients with severe genetic defects. Clinical gene therapy trials of X-linked severe combined immunodeficiency or adenosine deaminase deficiency have demonstrated the success and potential benefit of the therapy. Nevertheless, the complexity of the therapeutic products and their biological origin, as well as virus-related safety concerns require the need of a strict regulatory framework in order to guarantee the quality of the individual products and safety of the patients. The aim of this review is to give an overview of the rapidly evolving regulatory framework of Advanced Therapy Medicinal Products in Europe. We will summarize the most important regulatory documents to be considered before entering the clinical development phase – not only from a German but also from a European perspective.

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Сергеевичева В. В.1, Шевела Е. Я.1, Сизикова С. А.1, Кулагин А. Д.2, Крючкова И. В.1, Гилевич А. В.1, Лисуков И. А.2,
Козлов В. А.1, Останин А. А.1, Черных Е .Р.1

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Авторы [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [ORGANIZATION_RU] => Array ( [ID] => 26 [TIMESTAMP_X] => 2015-09-02 18:01:20 [IBLOCK_ID] => 2 [NAME] => Организации [ACTIVE] => Y [SORT] => 500 [CODE] => ORGANIZATION_RU [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 26 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13763 [VALUE] => Array ( [TEXT] => <p class="bodytext"><sup>1</sup>Институт клинической иммунологии СО РАМН, Новосибирск, Россия <br /><sup>2</sup>Новосибирский государственный медицинский университет, Новосибирск, Россия </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

1Институт клинической иммунологии СО РАМН, Новосибирск, Россия
2Новосибирский государственный медицинский университет, Новосибирск, Россия

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Мезенхимальные стромальные клетки (МСК), выделенные из костного мозга, обладают иммунорегуляторной активностью и способны поддерживать гемопоэз. К сожалению, данные, характеризующие биологические свойства МСК при различных патологических состояниях, очень немногочисленны и зачастую противоречивы. В настоящей работе мы показали, что МСК, полученные из костного мозга больных гемобластозами, имеют морфологию фибробластоподобных клеток и характерный фенотип. Более того, МСК больных обладают хорошо выраженной способностью к стимуляции гемопоэза, в сочетании со сниженным иммуносупрессорным потенциалом. Эти свойства МСК послужили основанием для клинического применения котрансплантации аутологичных гемопоэтических стволовых клеток и МСК в онкогематологии с целью ускорения восстановления гемопоэза. Нами были исследованы безопасность и гемопоэтические эффекты мезенхимальных стромальных клеток у пациентов с гемобластозами, которым выполнялась трансплантация периферических стволовых кроветворных клеток (ПСКК). Использование ex vivo  культивированных МСК, котрансплантированных с аутологичными ПСКК, позволило нам выявить снижение периодов критической нейтропении и тромбоцитопении у больных гемобластозами после высокодозной химиотерапии. Полученные результаты демонстрируют возможность и безопасность совместных трансплантаций МСК и ПСКК. Сокращение периода восстановления кроветворения свидетельствует  о позитивном влиянии МСК на гемопоэз.

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Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

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1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Organization [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_EN] => Array ( [ID] => 39 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Description / Summary [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 39 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13783 [VALUE] => Array ( [TEXT] => <p class="bodytext">Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.</p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.

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Autologous mesenchymal stromal cells of hemoblastosis patients efficiently support hematopoietic recovery after stem cell transplantation

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Vera V. Sergeevicheva1, Ekaterina Y. Shevela1, Svetlana A. Sizikova1, Alexander D. Kulagin2, Irina V. Kruchkova1,
Andrey V. Gilevich1, Igor A. Lisukov2, Vladimir A. Kozlov1, Alexander A. Ostanin1, Elena R. Chernykh1

1Institute of Clinical Immunology SB RAMS, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia

Mesenchymal stromal cells (MSCs) derived from bone marrow possess immunoregulatory activity and are able to support hematopoiesis. Unfortunately, data concerning the biological properties of MSCs in various pathologies is poor and often discrepant. In this study, we demonstrated that MSCs derived from bone marrow of patients with hemoblastoses have fibroblast-like morphology and a typical phenotype. Moreover, the patients' MSCs possess well-defined hematopoietic-supporting activity coupled with decreased immunosuppressive potential. These properties prove the clinical application of co-transplantation of autologous hematopoietic stem cells and MSCs in oncohematology to achieve a rapid hematopoietic recovery. Therefore we investigated the safety and hematopoietic effects of MSCs in patients with hematological malignancies receiving peripheral blood hematopoietic stem cell (PBSC) transplantation. We revealed the decreasing of the period of neutropenia and thrombocytopenia in the patients with hematological tumors after high-dose chemotherapy, when autologous PBSC were co-transplanted with ex vivo expanded autologous MSCs. Our results show that co-transplantation of autologous MSCs with PBSC is feasible and safe. The shortening of hematopoietic recovery time suggests that MSC may have a positive impact on hematopoiesis.

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Саша Ланге, Аксель Цандер, Клаудиа Ланге

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Мезенхимные стволовые клетки  человека (МСКЧ) в настоящее время интенсивно изучаются на предмет их потенциального применения в качестве средства клеточной терапии в регенеративной медицине. Их можно легко выделять, например, из костного мозга посредством залипания на пластике, и размножать in vitro. Представленные видеокадры показывают пролиферацию МСКЧ,  их взаимодействия между собой и процесс их деления.  Высокая степень подвижности МСКЧ может быть причиной возможных нарушений формирования «чистых» клонов даже при низкой плотности посева клеток.

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Sascha Lange, Axel R. Zander, Claudia Lange

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Author [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [ORGANIZATION_EN] => Array ( [ID] => 38 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Organization [ACTIVE] => Y [SORT] => 500 [CODE] => ORGANIZATION_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 38 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13860 [VALUE] => Array ( [TEXT] => <p class="bodytext"> Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany<br> <br> <b>Correspondence: </b><br> Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.gpperkiDyoi2yrm1leqfyvk2hi');">cllange@<span style="display:none;">spam is bad</span>uke.uni-hamburg.de</a> </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany

Correspondence:
Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: cllange@spam is baduke.uni-hamburg.de

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Human mesenchymal stromal cells (hMSC) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. They can be easily isolated, e.g., from bone marrow by plastic adherence, and expanded in vitro. These videos show the proliferation of hMSC, and how they interact with each other and divide. The large distances hMSC can conquer call into question the cloning carried out by low-density seeding.

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The MSCs' in vitro community: where to go?

Sascha Lange, Axel R. Zander, Claudia Lange

Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany

Correspondence:
Claudia Lange, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany, E-mail: cllange@spam is baduke.uni-hamburg.de

Human mesenchymal stromal cells (hMSC) are presently being investigated extensively for their potential use as cellular therapeutics in regenerative medicine. They can be easily isolated, e.g., from bone marrow by plastic adherence, and expanded in vitro. These videos show the proliferation of hMSC, and how they interact with each other and divide. The large distances hMSC can conquer call into question the cloning carried out by low-density seeding.

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Вебер К., Фезе Б.

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За последние годы произошла революция в области проточной цитометрии, в связи с внедрением компьютерной обработки данных и средств анализа, что облегчает одновременное изучение десяти и более параметров. В то же время некоторые средства, представления данных, предлагаемые коммерческими поставщиками, остались удивительно „старомодными“. Это приводит к странной ситуации, в которой высококачественные данные часто представлены низкокачественными иллюстрациями, а именно в виде точечных (пиксельных) построений. В особенности, данные, полученные с применением программного продукта FACSDiva часто отображаются рисунками в виде низкоразрешающей пиксельной графики, что приводит к изображениям плохого качества. К тому же, даже новейшая версия, Diva_6.1.2, все еще неспособна совместить две или несколько гистограмм в одну картину ("наложенная гистограмма") – популярное и убедительное средство прямого сравнения данных. В связи с этим, мы предлагаем легкий и практичный набор программных средств (Diva-Fit) для улучшения рисунков, продуцируемых с помощью программы Diva, которая облегчает создание высокоразрешающих графиков на основании данных, полученных посредством пакета FACSDiva. Кроме того, Diva-Fit дает возможность легкого удаления нежелательных квадрантных меток без ухудшения качества рисунков по данным проточной цитометрии.       

Наконец, мы показываем, что Diva-Fit поддерживает функцию построения наложенных гистограмм. Для работы с Diva-Fit необходимы следующие программные продукты: BD-FACSDiva 6.1.2; (2) PDF Creator 0.95; (3) Adobe Acrobat Reader, версия 9.1.0.  или более новая; (4) GIMP 2.6.4. для создания наложений для гистограмм; (5) Inscape 0.46 для удаления излишнего текста внутри рисунков. Отмечается относительная сложность работы с (4) и (5).  Важно отметить что все программные средства необходимы для Diva-Fit доступны бесплатно. Мы считаем, что предлагаемый набор программных средств может быть очень полезным для многих исследователей, работающих в области проточной цитометрии. [TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Описание/Резюме [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [DOI] => Array ( [ID] => 28 [TIMESTAMP_X] => 2016-04-06 14:11:12 [IBLOCK_ID] => 2 [NAME] => DOI [ACTIVE] => Y [SORT] => 500 [CODE] => DOI [DEFAULT_VALUE] => [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 80 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 28 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => [USER_TYPE_SETTINGS] => [HINT] => [PROPERTY_VALUE_ID] => 13942 [VALUE] => 10.3205/ctt-2009-en-000045.01 [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => 10.3205/ctt-2009-en-000045.01 [~DESCRIPTION] => [~NAME] => DOI [~DEFAULT_VALUE] => ) [AUTHOR_EN] => Array ( [ID] => 37 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Author [ACTIVE] => Y [SORT] => 500 [CODE] => AUTHOR_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 37 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13953 [VALUE] => Array ( [TEXT] => <p>Kristoffer Weber, Boris Fehse</p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Kristoffer Weber, Boris Fehse

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Author [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [ORGANIZATION_EN] => Array ( [ID] => 38 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Organization [ACTIVE] => Y [SORT] => 500 [CODE] => ORGANIZATION_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 38 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 13963 [VALUE] => Array ( [TEXT] => <p class="bodytext">Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany </p> <br/> <p class="bodytext"><b>Correspondence:</b><br> Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany<br> Phone: +49-40-7410-52705 / +49-40-7410-55518<br> E-mail: <a href="javascript:linkTo_UnCryptMailto('qempxs.o2aifivDyoi2hi');">k.weber@<span style="display:none;">spam is bad</span>uke.de</a> or <a href="javascript:linkTo_UnCryptMailto('qempxs.jilwiDyoi2hi');">fehse@<span style="display:none;">spam is bad</span>uke.de</a> <sup><br /></sup> </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

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In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.

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Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software

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Kristoffer Weber, Boris Fehse

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

In recent years, flow cytometry has been revolutionized via the introduction of digital data acquisition and analysis tools that facilitate simultaneous investigation of ten or more parameters. At the same time, some data presentation tools offered by commercial suppliers have remained surprisingly “antiquated”. This leads to the ironic fact that high-quality data is often represented by poor-quality illustrations: namely pixelated plots. In particular, data obtained using FACSDiva software is frequently exported into figures as low-resolution pixel graphics resulting in low-quality images. Additionally, even the newest version, Diva_6.1.2, is still unable to generate histogram overlays, a popular and convincing tool for direct data comparison. We hereby present an easy and down-to-earth Diva-Figure-improvement toolbox (Diva-Fit), which facilitates the generation of high-resolution graphs based on data acquired with FACSDiva software. Moreover, Diva-Fit allows the easy removal of unwanted quadrant labels without impairing the quality of FACS plots. Finally, we show that Diva-Fit supports straightforward composition of histogram overlays. All software tools necessary are freely available. We believe that the proposed toolbox may be very useful for many researchers working with flow cytometry.

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Вебер К., Фезе Б.

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Diva-Fit: поэтапное руководство к построению графиков и гистограмм с высоким разрешением для анализа данных проточной цитометрии, полученных посредством пакета программ FACSDiva. Дополнение.

На английском языке

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Kristoffer Weber, Boris Fehse

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Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Organization [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_EN] => Array ( [ID] => 39 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Description / Summary [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 39 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 14075 [VALUE] => Array ( [TEXT] => <p class="bodytext"> <strong>Here we describe all procedures depicted <a target="_blank" href="http://www.cttjournal.com/en/archive/tom-1-nomer-4/metody/diva-fit-poetapnoe-rukovodstvo-k-postroeniyu-grafikov-i-gistogramm-s-vysokim-razresheniem-dlya-anali/"><u>in the named article</u></a> in more detail.<br> </strong><br> <strong>Part 1:</strong> How to extract high-resolution dot plots and histograms from FACSDiva<br> <strong>Part 2:</strong> How to generate histogram overlays (based upon Part 1)<br> <strong>Part 3:</strong> How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1) </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Here we describe all procedures depicted in the named article in more detail.

Part 1: How to extract high-resolution dot plots and histograms from FACSDiva
Part 2: How to generate histogram overlays (based upon Part 1)
Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)

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Diva-Fit: A step-by-step manual for generating high-resolution graphs and histogram overlays of flow cytometry data obtained with FACSDiva software – Supplementary material

Download PDF version

Kristoffer Weber, Boris Fehse

Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Germany


Correspondence:
Research Dept. Cell and Gene Therapy, Clinic for Stem Cell Transplantation, UCCH, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Phone: +49-40-7410-52705 / +49-40-7410-55518
E-mail: k.weber@spam is baduke.de or fehse@spam is baduke.de

Here we describe all procedures depicted in the named article in more detail.

Part 1: How to extract high-resolution dot plots and histograms from FACSDiva
Part 2: How to generate histogram overlays (based upon Part 1)
Part 3: How to delete quadrant labels (Q1–Q4) within dot plots (based upon Part 1)

Hematology review

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Николай Н. Мамаев

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Обзор посвящён анализу сложных проблем современной цитогенетической и молекулярной диагностики Ph–позитивных (Ph+) лейкозов, их лечению в эру блокаторов тирозин-киназ (БТК) и аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК). Весомое место в обзоре уделено проблемам мутационного статуса вновь образованного гена ABL-BCR и большой вариабильности транскрибируемых с него молекулярных продуктов. Несмотря на то, что малый транскрипт (e1a2), ответственный за образование белка р190, свойственен большинству больных Ph+ ОЛЛ (как взрослых, так и у детей), он  встречается также у четверти больных хроническим миелолейкозом (ХМЛ). Наоборот, ответственные за продукцию  более крупного, характерного для большинства больных ХМЛ р210 протеина, e13a2 и e14a2 транскрипты имеют место также у четверти больных с Ph+ ОЛЛ. Наконец,  у 3% – 19% наблюдений оба транскрипта могут быть представлены одновременно. С другой стороны, появились данные о большом количестве точечных мутаций различных участков гена ABL-BCR, в том числе у нелеченых ранее больных. Большинство этих мутаций, за исключением  T315I и F317L, на результатах терапии Ph+ лейкозов БТК отражается мало, в то время при наличии в клетках отмеченных выше двух мутаций резистентность к терапии БТК становится доминирующей. 

Одним из важных моментов большого успеха аллоТГСК при Ph+ лейкозах является высокая чувствительность Ph+ клеток к антилейкемическому действию транс-плантата и к вливаемым донорским лимфоцитам. Несмотря на это, в эру активного использования в клинике БТК аллоТГСК при  ХМЛ отошла на второй план, не утратив своего излечивающего значения у плохо переносящих БТК или резистентных к ним больных. В отличие от ХМЛ, аллоТГСК у больных с Ph+ ОЛЛ должна проводиться без проволочек, причём крайне желательно в состоянии полноценной ремиссии (т. е. без признаков минимальной остаточной болезни). Для достижения этой цели всех больных с Ph+ ОЛЛ желательно направлять в хорошо оборудованные специализированные центры сразу же после постановки диагноза, поскольку только с использованием современных цитогенетических и молекулярно-биологических методик имеются реальные возможности: а) для лучшего контроля эффекта лечения желательной комбинации высокодозной химиотерапии и БТК, б) для выбора наилучших режимов кондиционирования и профилактики РТПХ; и, наконец, в) для оценки реального прогноза этих заболеваний.

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Nikolay N. Mamaev

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St. Petersburg Pavlov State Medical University, St. Petersburg, Russia


Correspondence:
Nikolay N. Mamaev, Clinical-laboratory Diagnostics Chair, Cytogenetic Lab, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 198022, Russia
Phone: +7 (812) 233-12-43 (office) or +7 (812) 726-53-25 (home)
E-mail: nikmamaev@spam is badrambler.ru

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The review is devoted to the complex problems of modern cytogenetic and molecular diagnostics of Ph-positive leukemias, their treatment in era tyrosine kinase inhibitors and hematopoietic stem cell transplantation at the condition of cytogenetic and molecular monitoring.

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Ph-positive leukemias in the era of modern cytogenetics, molecular biology, tyrosine kinase inhibitors and hematopoietic stem cell transplantation

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Nikolay N. Mamaev

St. Petersburg Pavlov State Medical University, St. Petersburg, Russia


Correspondence:
Nikolay N. Mamaev, Clinical-laboratory Diagnostics Chair, Cytogenetic Lab, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 198022, Russia
Phone: +7 (812) 233-12-43 (office) or +7 (812) 726-53-25 (home)
E-mail: nikmamaev@spam is badrambler.ru

The review is devoted to the complex problems of modern cytogenetic and molecular diagnostics of Ph-positive leukemias, their treatment in era tyrosine kinase inhibitors and hematopoietic stem cell transplantation at the condition of cytogenetic and molecular monitoring.

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А. И. Неворотин

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Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Организации [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_RU] => Array ( [ID] => 27 [TIMESTAMP_X] => 2015-09-02 18:01:20 [IBLOCK_ID] => 2 [NAME] => Описание/Резюме [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_RU [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 27 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 14203 [VALUE] => Array ( [TEXT] => <p class="bodytext">Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином <i>автор</i> обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Автор этой небольшой статьи, а заодно и специальной книги на соответствующую тему [1], всегда отдавал себе отчет в том, что презентация рукописи научного исследования в редакцию зарубежного журнала влечет за собой не только адекватное знание английского языка, но и высокий уровень научных результатов, а также весьма своеобразный, с точки зрения моего соотечественника, стиль их изложения. Эти предпосылки авторского успеха, неразрывно связаны между собой. Вот почему даже самые новые и интересные, но недостаточно аргументированные и неясно изложенные в рукописи результаты могут быть безоговорочно отклонены редакцией как недостоверные, а при скверном переводе как непонятные. В настоящей работе рассмотрены все эти три предпосылки в последовательности – оценка уровня исследования, стиль изложения результатов и перевод рукописи научной статьи (НС), планируемой к отправке в англоязычное периодическое издание. При этом некоторое внимание уделено все еще заметным, несмотря на глобализацию, особенностям мировосприятия отечественного и англоязычного ученого, что может как способствовать успеху в судьбе рукописи НС, так и в противном случае смягчит боль разочарования при неудаче путем указания на более подходящий путь при последующих попытках. Ведь отправляя рукопись на чужбину, автор, будь он русский, финн или японец, должен четко осознавать, что его творение оказывается «в чужом монастыре», причем «со своим уставом», которому и следует подчиниться, а если не устраивает – стоит ли тратить силы на попытку? Для удобства изложения здесь и далее термином автор обозначен как единственный исследователь и потенциальный автор будущей НС, так и соавторский тандем  или группа исследователей, объединенных общей целью опубликовать свои результаты на страницах англоязычного периодического издания, включая данный журнал.

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Alexey Nevorotin

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I. P. Pavlov Medical University, St. Petersburg, Russia

[TYPE] => HTML ) [~DESCRIPTION] => [~NAME] => Organization [~DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) ) [SUMMARY_EN] => Array ( [ID] => 39 [TIMESTAMP_X] => 2015-09-02 18:02:59 [IBLOCK_ID] => 2 [NAME] => Description / Summary [ACTIVE] => Y [SORT] => 500 [CODE] => SUMMARY_EN [DEFAULT_VALUE] => Array ( [TEXT] => [TYPE] => HTML ) [PROPERTY_TYPE] => S [ROW_COUNT] => 1 [COL_COUNT] => 30 [LIST_TYPE] => L [MULTIPLE] => N [XML_ID] => 39 [FILE_TYPE] => [MULTIPLE_CNT] => 5 [TMP_ID] => [LINK_IBLOCK_ID] => 0 [WITH_DESCRIPTION] => N [SEARCHABLE] => N [FILTRABLE] => N [IS_REQUIRED] => N [VERSION] => 1 [USER_TYPE] => HTML [USER_TYPE_SETTINGS] => Array ( [height] => 200 ) [HINT] => [PROPERTY_VALUE_ID] => 14208 [VALUE] => Array ( [TEXT] => <p class="bodytext">The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term <i>author</i> will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal.

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Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с <i>апоптозом</i> (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки. </p> <h3>Стиль</h3> <p class="bodytext"> Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями. </p> <h3>Заглавие</h3> <p class="bodytext"> Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков. </p> <h3>Введение </h3> <p class="bodytext"> Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность. </p> <h3>Материал и методика. Результаты</h3> <p class="bodytext"> В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка. </p> <h3>Обсуждение</h3> <p class="bodytext"> Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале. </p> <p class="bodytext"> Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе). </p> <h3>Перевод</h3> <p class="bodytext"> Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.<br> <br> •    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте <a href="http://www.senglish.narod.ru/books.html" target="_blank"><u>http://www.senglish.narod.ru/books.html</u></a><u>.</u> <br> <br> •    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности. <br> <br> •    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.<br> <br> •    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом. <br> <br> •    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала. </p> <h3>Литература</h3> <p class="bodytext"> 1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001. </p> <p class="bodytext"> 2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963. </p> <p class="bodytext"> 3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501. </p> <p class="bodytext"> 4. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0R-4M7CMHV-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a08a9319307df8c31ab91f8edb83231b" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004</u></a>. </p> <p class="bodytext"> 5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8. </p> <p class="bodytext"> 6. <a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSS-4183951-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5bbd5567c24ff8458d03ad14bd2c9ef8" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2</u></a>.  </p> <p class="bodytext"> 7. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33122/?tool=pubmed" title="Opens external link in new window" target="_blank" class="external-link-new-window"><u>Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198</u></a>. </p> <p class="bodytext"> 8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр.  </p> <p class="bodytext"> 9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.<br> </p> <p class="bodytext"> 10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Уровень исследования

На первый взгляд представляется очевидным, что при решении редколлегии соответствующего журнала в пользу или против публикации рукописи НС, самым существенным критерием ценности результатов является новизна. Во всяком случае, для нашего автора, а возможно и большинства отечественных изданий, уровень новизны является решающим, если не единственным фактором в определении судьбы рукописи. Однако, для англоязычного журнала сугубо феноменологический аспект исследования, т.е. получение новых данных или подтверждение (опровержение) ранее описанных, может оказаться не единственным достоинством, позволяющим принять решение о публикации. Нужны еще полноценные cвидетельства с использованием признанных методик и более того, четко изложенная интерпретация полученных результатов в системе уже известных и опубликованных сведений в данной области. Скорее всего, именно слабостью доказательной базы для новых данных (из-за устарелого оснащения) и научной аргументации (из-за отсутствия отечественных программ по языку науки), работы моих соотечественников по биологии и медицине так редко публикуют в зарубежных (кроме стран СНГ) изданиях, а если такое и происходит – то почти всегда в соавторстве с зарубежными коллегами. Наглядным показателем исключительной роли убедительности доказательств и искусства интерпретации может служить пример с апоптозом (запрограммированная смерть клетки). Сам феномен апоптоза, его распространенность, понимание его сущности в целом и даже термин был признан более трех десятилетий назад [2,3] что подтверждалась в тысячах солидных публикаций. Тем не менее, нобелевская премия в области физиологии или медицины (Nobel Prize in Physiology or Medicine) за 2002 г была присуждена не первооткрывателям или кому-то из их многочисленных последователей, а лишь троим выдающимся ученым,-  Sydney BRENNER, John SULSTON и Robert HORVITZ, которым на безупречной экспериментальной модели впервые удалось расшифровать на молекулярном уровне ключевые признаки этого феномена и тем самым с высокой достоверностью окончательно установить его фундаментальную роль в важнейших физиологических и патологических процессах. Для нашего исследователя такое решение может показаться несправедливым, поскольку налицо пренебрежение царившим веками правом научного приоритета. Однако, современные реалии, включая жесткую конкуренцию, а также случаи ошибок и даже фальсификации результатов, при всем уважении к первооткрывателям, заставляют считаться не только с приоритетом, но и с такими параметрами научного исследования, как мощность доказательной базы и определение достойного места для неизвестного ранее феномена среди уже изученных фактов в данной, а по-возможности и смежных дисциплинах. Во всяком случае, не только в самых передовых (например, Nature; Science; PNAS), но и в менее престижных изданиях рукопись новаторской работы без солидных доказательств и теоретических обоснований скорее всего будет хотя и очень вежливо, но все же отклонена сразу же после или даже без рассмотрения рецензентами . И не следует обижаться или, хуже того, рассматривать отказ как проявление дискриминации к россиянам: просто ни один зарубежный журнал, при молчаливой поддержке мирового научного сообщества, не будет рисковать своей репутацией, выпуская в свет научную работу невысокого качества. Одним словом, чем более совершенна во всех смыслах научная продукция, в частности НС, тем выше ее цена, точно также как в экономике, если сравнивать некоторые виды сырья, например, нефти, леса или руды и т.п. (=комплекты новых данных на уровне НС) с таковыми после их грамотной обработки.

Стиль

Под этим понятием здесь подразумеваются определенная последовательность, относительный объем и расстановка отдельных частей материала в типовой (regular) НС. Как в зарубежном, так и отечественном журнале налицо одни и те же разделы, несколько варьировать может лишь порядок их расположения в НС. Опыт регулярного чтения англоязычных журналов позволяет мне сделать ряд осторожных обобщений по основным разделам НС, отметив при этом характерные различия в сравнении с отечественными моделями.

Заглавие

Хотя таковое в общем виде отражает содержание НС как в отечественных, так и в зарубежных научных журналах, у «нас» название зачастую бывает череcчур уж общим и потому расплывчатым, в частности, из-за таких оборотов как «Некоторые особенности…», «Клиническое (биохимическое; молекулярно-биологическое) исследование (анализ, характеристика)…». Поскольку каждая из таких версий как правило имеет несметное количество вариантов, трудно понять, о чем именно идет речь. У «них» неясность в формулировке заглавия практически исключена, причем по названию НС читатель даже до знакомства с текстом может весьма точно определить как объект, так и «изюминку» работы. В этом смысле очень эффективным приемом прояснения сути работы до ее прочтения (примерно в 15% англоязычных публикаций) является разделение заглавной фразы двоеточием (слева – предмет исследования, а справа – главный итог или кредо автора), а также вопросительная форма заголовка (постановка задачи с предсказуемым ответом). Далее, сугубо художественно-литературным «перегибом» можно, на мой взгляд, считать введение элементов юмора, а также чрезмерной или даже рискованной образности в заглавиях [4-6]. Несмотря на истинное остроумие образцов, свободных от вульгарности [7], можно легко пожертвовать такими «украшениями» и последовать общепринятому правилу составления предельно ясных заголовков НС без примитивных трюков.

Введение

Данный раздел регулярной англоязычной НС, помимо постановки задачи (этого  придерживаются и в наших журналах), содержит также лаконичную и в то же время исчерпывающе соразмерную с масштабом задачи историю вопроса (у «нас» слишком уж краткую, скорее всего из-за лимитов места у данного журнала), а также, в самом конце – краткое, в одной – двух фразах, изложение основных результатов (у «нас» это начали практиковать лишь недавно, далеко не везде и не всегда удачно). Проанализировав множество публикаций в самых различных областях биологии и медицины, я пришел к заключению о том, что англоязычная, в отличие от отечественной публикации преследует, помимо презентации новых данных, также и образовательную цель. В результате, во введении любой читатель, даже студент с достаточным сроком базисного обучения, может понять в общих чертах очень сложную незнакомую проблему и тем самым заинтересоваться новым для него материалом. Как это достигается? НС обычно начинается с какого-либо известного, просто изложенного и потому легко понятного утверждения, имеющего лишь самое общее отношение к предмету работы. Гармоничная, сдобренная цитированиями, концентрация фактов вокруг нерешенной проблемы постепенно выводит читателя к цели исследования, а краткий итог, усиленный ссылкой на методику, ненавязчиво дает понять не только основной итог работы, но также и то, стоит ли проявить дальнейший интерес к данной тематике и даже тратить время на то, чтобы дочитать НС до конца. Таким образом, хорошая НС это как источник новых фактов и идей, так еще и мини-лекция, помогающая читателю быстро пополнить знания и выбрать свое индивидуальное направление. К глубокому сожалению, отечественный автор, хочется верить что только по причине дефицита места, сразу же начинает свой труд с описания слишком сложных, иногда «мудреных» и понятных только ему (загадочная русская душа?) деталей проблемы, что автоматически снижает круг читателей и возможных последователей. Tакой подход при подаче работы в зарубежный журнал может привести (в лучшем случае) либо к жесткой критике со стороны рецензентов или (скорее всего) к отказу в публикации в англоязычном журнале с прозрачным намеком на некомпетентность.

Материал и методика. Результаты

В англоязычной научной периодике оба эти раздела настолько четко систематизированы и стандартизованы, что нам останутся лишь подыскать подходящий прототип англоязычной работы и по ее шаблону (лучше, по нескольким шаблонам) вводить полученные данные. Естественно, что только свои, чтобы исключить любые подозрения в плагиате. Ясно также, что успешное решение указанной задачи по силам только начитанному автору с достойным запасом статей-прототипов и хорошим знанием английского языка.

Обсуждение

Этой части НС надлежит по определению быть наиболее пространным и к тому же самым трудным разделом как для авторского творчества, так и для полноценного восприятия читателем.. По моим приблизительным подсчетам, в англоязычных изданиях обсуждение является и самым пространным текстом, занимая до 40% всего объема НС. В отечественных же, даже очень респектабельных изданиях эта цифра редко превышает 20%, причем обсуждение как правило ограничено обобщенной формулировкой полученных данных, подтверждением своей правоты путем немногих ссылок на единомышленников (как правило, с уклонением от спора с инакомыслящими, а в противном случае – с их полным разгромом) и с одностороннем (только в свою пользу!) заключением. А где же искусная цепь аргументов как «за», так и «против» своей концепции, с допущениями о пока еще недостаточном совершенстве примененных методик и даже о частичной правоте оппонентов? Почему так мало ссылок (в англоязычном издании на раздел Обсуждение регулярной НС приходится как правило большинство цитирований) и что помешало автору при заявлении об готовности к дальнейшей работе наметить хотя бы ее примерное направление? Тот, кто сможет преодолеть обозначенные выше недостатки и восполнить соответствующие пробелы, сможет своими глазами убедиться, насколько оправданными оказались усилия, затраченные на то, чтобы возрадоваться, увидев свою работу опубликованной в англоязычном журнале.

Все сказанное здесь отражает исключительно мою точку зрения, которая может быть дополнена, а также частично или даже существенно изменена более опытным и проницательным последователем, посвятившим свою жизнь не только научной работе, но и поиску путей адекватного представления ее результатов средствами англоязычной периодики. (Замечу в скобках, что первая половина этой фразы, помимо очевидной смысловой нагрузки, представлена здесь как наглядный пример этикета, принятого в зарубежном научном сообществе).

Перевод

Ниже предлагаются пять ключевых и поверенных опытом рекомендаций относительно стратегии перевода рукописи НС на английский язык.

•    Для переводчика, знание грамматики английского языка, особенно глагольных форм, должно быть на уровне не ниже одного из лучших наших учебников [8]; могут оказаться полезными и другие издания, список которых легко найти на сайте http://www.senglish.narod.ru/books.html.

•    Помимо минимального словарного запаса (1500 или более слов), для переводчика необходимы также словари по специальности, например, по медицине [9]. Отметим, однако, что к своему удивлению, многих нужных терминов автор там не найдет, поэтому надо еще завести и регулярно пополнять ряд персональных мини-словарей по своей узкой специальности.

•    Еще большую проблему проблему может представить грамотное внедрение нужного слова в данную фразу или оборот. В такой ситуации проблему поможет решить недавно выпущенный Collins COBUILD dictionary на CD-ROM, который содержит множество фраз-прототипов. Мой сборник [1] инонимов, тогда как последующие издания «преуспели» в обратном, сделав поиск синонимов весьма нудным занятием.

•    Очень эффективным подходом к составлению фраз и оборотов для рукописи НС представляется поиск прототипов через файлы переводчика, содержавшие по 200-250 резюме к англоязычным статьям (по 2-3 МВ на файл). Имея перед глазами (или в уме) текст русскоязычной фразы, переводчик просканирует свои файлы c использованием ключевого англоязычного слова (Ctrl+F) до того момента, пока наконец не отыщет наиболее подходящий оборот. За этим должна последовать тщательная подгонка прототипа под конечный продукт. В высшей степени ценными могут оказаться также тексты целых статей, обработанные  аналогичным способом.

•    До какой же степени (если и вовсе реально) можно рассчитывать на профессионального филолога как на потенциального переводчика русскоязычной рукописи НС на английский язык? Всецело, но при условии, что такой специалист компетентен и в той конкретной области науки, с которой имеет дело данная работа. Однако эти два столь различных мастерства очень редко могут со-существовать на равных у одного и того же человека. Поэтому оптимальным представляется более или менее любительский перевод ученого с навыками регулярного чтения по-английски и с рядом обозначенных выше «домашних» заготовок. Выполненная таким образом, но все еще «сырая» работа могла бы быть доведена до совершенства с привлечением и доминирующим участием филолога-профессионала.

Литература

1. Неворотин АИ. Матричный фразеологический сборник. Пособие по написанию научной статьи на английском языке. СПб, СпецЛит. 2001.

2. Weedon D, Searle J, Kerr JF. Apoptosis. Its nature and implications for dermatopathology. Am J Dermatopathol. 1979;1(2):133-44. pmid: 44963.

3. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306. pmid: 7014501.

4. Arshavsky YI. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation? Prog Neurobiol. 2006;80(3):99-113. doi: 10.1016/j.pneurobio.2006.09.004.

5. Putney JW. “Kissin’ cousins”: intimate plasma membrane-ER interactions underlie capacitative calcium entry. Minireview. Cell. 1999;99:5-8.

6. Stevens CF. A million dollar question: does LTP = memory? Minireview. Neuron. 1998;20:1-2. doi: 10.1016/S0896-6273(00)80426-2

7. Griffin DR. Animals know more than we used to think. Commentary. Proc. Natl. Acad. Sci. USA 2001;98:4833-4840. doi: 10.1073/pnas.091088198.

8. Израилевич ЕЕ, Качалова КН. Практическая грамматика английского языка с упражнениями и ключами. СПб, Каро. 2007. 608 стр. 

9. Англо-русский медицинский словарь (70000 терминов). - 4-е изд., стер. – М, Руссо. 2000.

10. Муравейская МС, Орлова ЛК. Английский язык для медиков: учеб. пособие для студентов, аспирантов, врачей и научных сотрудников. 2-е изд., М., Наука, 384 с. 1999.

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Research articles in English: what should be considered before submitting a manuscript

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Alexey Nevorotin

I. P. Pavlov Medical University, St. Petersburg, Russia

The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English–language journals invariably requires not only good English but also a high level of research and – in my compatriots’ view – a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites – the level of the results, style of content presentation, and language – will be considered in relation to research articles (RA) intended for submission to English–language journals. Special attention will be paid to the clear differences – despite globalization – in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal’s standards or not waste his/her efforts. As the Russian proverb states: “Nobody goes to another monastery with one's own charter.” For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript – this one included – to an English–language journal.

Forum

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Роберт М. Фредриксон

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Редактор журнала "Molecular Therapy", www.nature.com/mt

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Комментарий к статье Алексея И. Неворотина "Научные статьи на английском языке: что следует учитывать перед отправкой рукописи"

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Robert M. Frederickson

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Editor Molecular Therapy, www.nature.com/mt

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Commentary on Alexander Nevorotin, Research articles in English: what should be considered before submitting a manuscript

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Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале <i>Nature</i>, а потом – в изданиях той же группы - <i>Nature Medicine</i> и <i>Nature Biotechnology</i>. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается <i>Nature Group</i>. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований. <br>   <br> Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.<br> <br> Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени. <br> <br> Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе! <br> <br> Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией <i>Nai, Inc.</i>, находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг <i>NPG</i> также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении. <br> <br> Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору!  <br> <br> В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу. </p> [TYPE] => HTML ) [DESCRIPTION] => [VALUE_ENUM] => [VALUE_XML_ID] => [VALUE_SORT] => [~VALUE] => Array ( [TEXT] =>

Я прочел с большим интересом статью Неворотина, где даются советы тем исследователям из государств, находящихся на территории бывшего СССР, которые хотят, чтобы их работа была опубликована в западных англоязычных журналах. Я примерно 15 лет работал в качестве профессионального редактора журналов с биомедицинской тематикой, вначале – в журнале Nature, а потом – в изданиях той же группы - Nature Medicine и Nature Biotechnology. В течение последних 8 лет я был издателем  Molecular Therapy – официального журнала Американского Общества генной и клеточной терапии, который также издается Nature Group. Должен признать, что за это время через мое рабочее место прошли лишь несколько работ, отправленных из этого региона. Однако, по моему опыту,  Nature Group и, конечно, Molecular Therapy стремились быть восприимчивыми к научным статьям из этих регионов и стран Азии, в которых отмечается быстрый рост экономики и исследований.
 
Большинство редакторов понимает те дополнительные трудности, с которыми сталкиваются авторы, у которых английский язык не является родным. Эта проблема не ограничивается работами из исследовательских лабораторий в данных регионах, но может также повлиять на работу, отправленную теми стажерами-докторантами из этих стран, кто теперь работает на Западе, особенно если главный автор не проверил его (или ее) стиль письма. На мой взгляд, наиболее важен тот фактор, что такие авторы передают свою статью исследователю в области биомедицины, чей родной язык – английский, но который не вовлечен непосредственно в это исследование, или даже в специфическую манеру его изложения. Почему? Потому что исследователь, более удаленный от проекта, обычно может лучше обеспечить доступность для обычных читателей при своей манере письма, принимая во внимание, что эта работа направляется в журнал общего профиля с высоким рейтингом, в противоположность более специальным журналам, где читатели (и издатели) могут быть лучше знакомы с состоянием дел и жаргоном в конкретной области.

Действительно, эта последняя причина того, что многим авторам – как носителям, так и не носителям английского языка – не удается преуспеть в таких публикациях. При нарастающем объеме исследовательских статей, многие редакторы были завалены огромным числом рукописей, которые они должны просеивать.  Этот первичный редакторский отсев имеет целью определить, заслуживает ли работа внешнего рецензирования или она должна быть возвращена автору для отправки в другой журнал. На самом деле это может и так для профессиональных редакторов в журналах с более высоким ииндексом цитирования – тех из них, кто более не вовлечен активно в академическую или клиническую науку, и редакторы в журналах профильных обществ, которые, в основном, возглавляют активные исследовательские группы. Конкуренция в часто цитируемых журналах сурова. Шансы на принятие статьи могут быть порядка 10%. Редактор, по сути, должен стремиться выбрать среди множества рукописей, попадающих на стол к нему, те из них, которые соответствуют критериям потенциальных публикаций с высоким ндексом цитирования. Эти критерии, конечно, включают в себя новизну, научную строгость и высокое качество, но должны также содержать другой важный фактор. Вопрос для редактора состоит в том, будет ли эта работа интересной для широкого круга читателей; другими словами,  простирается ли цитируемость и общий интерес этих новым результатам за пределы специфической узкой области данного исследования. За эти последние критерии трудно ручаться, и они, конечно, весьма субъективны. Как раз по этой причине именно автор ответственен за то, чтобы подчеркнуть как можно более ясными словами, как для читателей, так и (наиболее важно) – для редактора, почему работа имеет общий научный интерес и значимость.  И помните, что редактор не читает данную работу в отдельности, а, скорее, как одну из кучи конкурирующих работ, которые он (или она) старается сделать как можно меньше за ограниченный период времени.

Именно в связи с этим я не могу удержаться от того, чтобы не вспомнить реакцию Наума Зонненберга, ученого из Университета Мак-Гилл - моего руководителя по докторской степени – на первый набросок моей первой рукописи, сделанной под его руководством: «Сделай ее проще. Люди и так уже вынуждены слишком много читать». Лишь спустя некоторое время понял, насколько глубоким был на самом деле этот, казалось, бы простой совет. Поскольку, если вы не можете объяснить ясно и просто, в нескольких словах, значение вашей работы, то и работа эта на самом деле, вероятно, не столь уж значима! Конечно, если вы хотите привлечь внимание редактора или кого-нибудь из работающих за пределами вашей области, то придерживайтесь краткости, четкости и простоты вашего текста и логического построения, что облегчит восприятие работы и оценку ее достоинств. Я всегда был несколько упорно-навязчивым и, поскольку представляю себе многих из тех, кто тяготел к научной карьере и сосредоточился на специфической проблеме. Если мы желаем ее понять, то это может ослепить нас в отношении более широкого контекста. В подробном описании нашей работы мы задаемся целью быть точными и глубокими, но это часто работает против нас, так как мы при этом можем потерять многих читателей, у которых может и не быть той же привязанности и интереса к нашей работе!

Конечно, большинство исследователей, физически находящихся в бывших странах Восточного блока или в Азии, могут и не иметь легкого доступа к коллегам, желающим посвятить им время, необходимое для помощи в написании научной статьи. В таких случаях может быть полезным положиться на помощь профессиональной редакторской службы. Такие группы в последние десятилетия помогали исследователям в Японии и других азиатских странах.  Услуги могут варьировать от простых исправлений грамматических ошибок, произношения и стилистики до более существенных и системных аспектов изложения, и они обычно должны обсуждаться непосредственно с поставщиком услуги. Я работал с компанией Nai, Inc., находящейся в Иокогаме с 2001 года, но там сейчас существует множество таких услуг, и собственная служба языковых услуг NPG также недавно вступила в игру. Я был бы счастлив направить хотя бы некоторых  читателей по этому вопросу в нужном направлении.

Далее, все не возражающие против этого редакторы различаются между собой по своему подходу и стилю. Вот почему наиболее важной вещью, которую может сделать автор, это непосредственно завладеть вниманием редактора. Этого можно добиться путем обсуждения Вашей работы с редактором на конференции или симпозиуме, или просто посылая ему сообщения по электронной почте или делая вызовы по телефону. Посылайте ей или ему абстракт работы, чтобы определить, соответствует ли работа политике журнала или будет ли она интересна читателям. Развитие отношений с редактором является, вероятно, лучшей вещью, которую автор может сделать, чтобы вникнуть в редакционный процесс и стандарты каждого конкретного журнала, и приобрести важную обратную связь по своей работе и стилю представления материала. Одна из вещей, которые я отмечал за многие годы, это – разнообразие подходов и личностей в невероятно противоречивом мире исследователей в биомедицинской области. Я всегда впечатлялся теми людьми, которые отказывались сдаваться при отклонении публикации и кто упорствовал в своем диалоге с редактором, активно стремился поддерживать обратную связь. Это - гораздо более конструктивный подход, нежели сухое электронное сообщение, игнорирование или полное молчание – ничто из этого не приносит пользу автору! 

В заключение отмечу, что исследователи из неанглоязычных регионов мира сталкиваются с теми же проблемами, что и англоговорящие авторы, также находясь в весьма конкурентной среде при публикации, но к этому добавляется необходимость усвоения особого стиля и подхода, обычных для западных журналов. Единственный способ научиться движению в этом окружении, это – просто спрыгнуть туда и получить несколько ударов, так как лишь приобретая опыт, путем проб и ошибок, автор может понять, что работает в его или в ее пользу.

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Scientific writing navigation: jump in and take a few hits

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Robert M. Frederickson

Editor Molecular Therapy, www.nature.com/mt