ISSN 1866-8836
Клеточная терапия и трансплантация

MP-06. Functional evaluation of telomeric complex genes in patients with myelodysplastic syndrome and acute myeloid leukemia

Ayrat M. Sadykov, Dmitriy S. Bug, Nikolay Yu. Tsvetkov, Ildar M. Barkhatov

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia

Contact: Ayrat M. Sadykov, phone: +7 (981) 895-19-46, e-mail:

doi 10.18620/ctt-1866-8836-2023-12-3-1-176


A decrease in the average telomere length, as well as changes in the functions of shelterin complex and telomerase (telomere complex) have been observed in various tumor diseases including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This is due to age-related clonal changes in myeloid progenitor cells in hematopoiesis. Changes in the function of the telomeric complex can contribute to tumor transformation, enabling tumor cells to evade a crisis caused by short telomeres. At the same time, it remains unclear by what mechanisms, in addition to acquired mutations, a tumor cell is able to evade the crisis of short telomeres in myeloproliferative diseases and maintain its proliferative potential. The purpose of our study was to investigate the values of key components of the telomere complex (telomere length, telomerase expression, and genes encoding shelterin complex proteins) in patients diagnosed with tumor transformation resulting in high-risk MDS or secondary AML aiming for evaluation of the role of telomere complex in this process.

Materials and methods

The study included 74 patients with MDS/AML, at the median age of 53 years (38-58) (see Table 1). The control group consisted of 37 healthy donors at a median age of 34 years (27-43). The average length of telomeres and the relative expression level of telomerase genes and proteins of the shelterin complex were evaluated using real-time PCR.


Statistically significant differences were found when comparing telomere length and expression levels of telomeric complex genes between patients and healthy donors. The median telomere length obtained for healthy donors was 5.8 kb (1.5-7.9). The expression levels of the genes were as follows: TRF1-210% (173-293), RAP1-297% (258-437) and TIN2-141% (93-158). The telomere length for patients is 1.3 kb. (0.8-3.2), TRF1-162% (125-207), RAP1-179% (117-398) and TIN2-80% (66-114) (p<0.05). In presence of higher numbers of undifferentiated blasts in bone marrow, there decreased expression levels were found for RAP1 (p=0.044), TIN2 (p=0.041), and TPP (p=0.015) genes. A similar trend was observed when assessing telomere lengths. The telomere lengths were relatively shorter in patients with a complex karyotype (p=0.022). Additionally, in patients with a deletion of the long arm of chromosome 5, the expression levels of the TRF2 gene were significantly reduced (p=0.045) compared to the group of patients without detectable cytogenetic aberrations. In patients with a transformation into high-risk MDS/secondary AML, there is a significant inverse correlation between the number of undifferentiated blasts in the bone marrow and components of telomeric complex: TRF2 (r=-0.444, p=0.019), RAP1 (r=-0.407, p=0.029), TERT (r=-0.556, p=0.003), and TRF2 (r=-0.673, p=0.0001), as well as telomere length (r=-0.419, p=0.019). This pattern was not observed in patients who did not show evolving tumor clones.


The obtained results demonstrated significantly changes in functioning of telomere complex genes, which may be considered an additional marker of tumor progression.


Telomere length, myeodysplastic syndrome, acute myeloid leukemia.

Table 1. Characteristics of patients

Supplement 12-3

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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