AL-02. Dynamics of the mRNA WT1, PRAME, EVI1, BAALC, and HMGA2 genes during therapy of acute promyelocytic leukemia
Alexey S. Gorbenko, Marina A. Stolyar, Varvara I. Bakhtina, Vladislav V. Galanin, Igor A. Olkhovskiy
National Medical Research Institute of Hematology, Krasnoyarsk Branch, Krasnoyarsk, Russia; Krasnoyarsk Research Center, Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia; Regional Clinical Hospital, Krasnoyarsk, Russia; V. F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia
Contact: Dr. Varvara I. Bakhtina, phone: +7 (923) 357-57-77, e-mail: doctor.gemat@gmail.com
Summary
The use of All-trans-retinoic acid (ATRA) has significantly improved the prognosis of patients with promyelocytic leukemia (APL). However, accurate monitoring of residual disease is still required for early detection of relapses. In recent years, promising results in the diagnosis of myeloid leukemia have been demonstrated by the use of chimeric transcripts, as well as mRNA of a some genes expressed by the non-differentiated cells. In this paper, we present the results of a following-up the patients with APL within a year after starting of the therapy which included idarubicin and ATRA.
Materials and methods
In bone marrow samples, along with quantitative determination of the PML::RARa chimeric transcript specific for APL, as well as mRNAs of five onco-associated genes were measured using allele-specific RT-PCR using the “Leukemia Monitor” and “Leukemia Screen” reagent kits.
Results
In all cases, high levels of PML::RARa expression were initially accompanied by increased level of WT1 mRNA and, quite often, with increase in PRAME mRNA, however, at low values of other mRNAs under study. At the end of consolidation treatment, the mRNA levels of PML::RARa and WT1 dropped sharply to undetectable values, but the mRNA levels of the HMGA2, EVI1, and BAALC genes proved to be significantly increased. Interestingly, over the next 9 months of follow-up, in presence of complete clinical and hematological remission and undetectable levels of the PML::RARa transcript, the dynamics of mRNA of other genes was different. HMGA2, EVI1, and BAALC mRNA levels remained high, whereas WT1 and PRAME levels were either below the detection limit or rose and remained stable, but did not reach the pre-treatment values. At the same time, the relative contribution of EVI1 expression in the dynamics of observations showed a steady decrease relatively to HMGA2 and BAALC expression.
Conclusion
The data obtained obviously reflect the individual features of polyclonal hematopoiesis recovered during the therapy. Calculating the relative contribution of individual low-specific mRNAs in APL monitoring provides an index independent on the absolute values thus reflecting total transcriptome profile of PMA::RARa-negative bone marrow cells. Further monitoring of patients will allow to assess a prognostic value of this diagnostic index.
Keywords
Acute promyelocytic leukemia, therapy effectiveness, monitoring, PML, RARa, HMGA2, EVI1, BAALC, WT1, PRAME.
