Dacogen treatment results of 8 MDS patients and 2 CMML patients (a course dose — 100 mg/m2) are presented. Hematological response according to modified IWG criteria (complete remission - 2 pts, bone marrow remission — 1 pts, disease stabilization — 4 pts) has been established in 70% of patients. Complete cytogenetic response has been achieved in one patient with secondary MDS and multiple chromosomal aberrations after 2 therapy courses. Complications because of which intercourse intervals elongated are registered in 3 patients. The obtained data demonstrated efficacy of Dacogen treatment for high risk MDS and CMML patients.

Detection of FLT3 gene mutations in acute myeloid leukemia is now recognized as an unfavorable factor that affects the disease course, emerging the risk of relapses and overall survival shortening and disease-free survival of patients. The aim of the study was to determine the frequency of mutations of the gene FLT3 and to assess their impact on clinical indicators, overall survival and disease-free survival in patients with acute myeloid leukemia. We compared complete blood count parameters, karyotype, duration of overall survival and disease-free survival in 199 patients with acute myeloid leukemia depending on the presence or absence of mutations of the FLT3 gene. Significant differences across these groups were discovered only in WBC and blasts between the group of patients with acute myeloid leukemia (FLT3+) and without mutations in the FLT3 gene (FLT3-). The differences between two groups were also identified in patients chromosomal aberrations. Significant differences (p=0,00024) in the duration of overall survival between groups of patients with acute myeloid leukemia with mutations of FLT3-ITD+, FLT3-TKD+ and FLT3- were demonstrated. Median overall survival was: 1 6 months for patients with mutation FLT3-ITD+ and 17 months for FLT3-TKD+ patients and not achieved for FLT3- patients. The use of modern molecular genetic methods of research in acute myeloid leukemia allows to improve the diagnosis of the disease, as well as to carry out risk stratification and individualize therapy. The use of targeted therapy for FLT3-positive patients who are not candidates for hematopoietic stem cell transplantation will increase the effectiveness of the treatment and improve the performance of overall survival and disease-free survival.

Monosomal karyotype is the extremely poor variant of chromosomal aberrations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Retrospective analysis of 43 AML and 33 MDS patients was performed to determine typical clinical and hematological features of chromosomal karyotype. No characteristics typical for monosomal karyotype were found. Median of overall survival of AML and MDS patients was 6 and 8 months accordingly. At the same time some patients had relatively favorable course of their disease.

AIM to investigate the methylation status of the SOX7 and p15NK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemia (AML) in order to assess the association of the rate of aberrant methylation (AM) with the morphological variant and pattern of chromosomal aberrations, as well as the impact of the methylation status on survival. SUBJECTS AND METHODS The data of 57 AML patients aged 20 to 79 years were analyzed. The methylation status of the genes was studied by methylation-specific polymerase chain reaction. RESULTS The signs of the AM of ≥1 gene were detected in 52 (91.2%) of the 57 patients. The most common finding was AM of simultaneously 2 or 3 genes: in 29.8 and 21.1% of the patients, respectively. Concurrent methylation of 3-5 genes proved to be a more frequent finding in AML patients with myelodysplasia: in 7 (70%) of 10 patients. The proportion of patients with methylation of 5 genes was considerably higher in a group of patients with a complex karyotype: 50% versus 8.3% among other patients (odds ratio: 11.0; 95% confidence interval 2.0 to 61.6; p=0.01). There were no differences in the median overall and relapse-free survival rates in patients with a normal karyotype and without FLT3 and NPM mutations, who received induction therapy, in relation to the number of genes with AM. CONCLUSION AM of the p15NK4b and SOX7 genes and Wnt signaling pathway antagonists is detected in the majority of patients with AML, which allows hypomethylating agents to be recommended for the treatment of patients who cannot use intensive cytostatic therapy for different reasons. The detection of a large number of genes with the aberrant methylation status in most AML patients with myelodysplasia or a complex karyotype serves as the basis for initiating trials to evaluate the efficiency of a combination of 5-azacytidine and cytostatics.

Метилирование генов-супрессоров опухоли рассматривают как один из ключевых механизмов развития миелодиспластического синдрома (МДС). С целью выявления ассоциации статуса метилирования генов SOX7, p15INK4b, SFRP1, SFRP4 и SFRP5 с отдельными клинико-гематологическими показателями и общей выживаемостью (ОВ) проанализированы данные 46 больных МДС, установленного по классификации ВОЗ. Медиана возраста больных 67,5 года. Статус метилирования генов изучали методом метилспецифичной ПЦР. Аберрантное метилирование одного и более генов обнаружено у 43 больных (93,5 %). С наибольшей частотой выявлялось метилирование SOX7 (84,8 % больных), SFRP1 (71,7 % больных) и p15INK4b (54,3 % больных). Метилирование одного, двух, трех, четырех и пяти генов одновременно имело место у 10,9 %, 28,3 %, 26,1 %, 19,6 % и 8,7 % больных, соответственно. Доли больных с аберрантным метилированием SFRP1, SFRP4, SOX7 и p15INK4b в группах, выделенных по процентному содержанию бластов в костном мозге, не различались. Метилирование гена SFRP5 было более частой находкой у больных рефрактерной анемией с избытком бластов (РАИБ): 43,5 % против 13,0 % у больных без избытка бластов; OR = 5,1, 95 %CI: 1,2–22,3, p = 0,047. У больных без бластоза чаще выявлялись случаи с 0–1 метилированным геном: 26,1 % против 8,7 % у больных РАИБ. В то же время, в группе больных РАИБ увеличение содержания костномозговых бластов сопровождалось увеличением числа случаев с 3–5 метилированными генами. В общей группе не обнаружено корреляции числа метилированных генов с возрастом, уровнем бластных клеток в костном мозге и вариантом кариотипа. Увеличение числа метилированных генов не влияло на ОВ. Сделано заключение об увеличении объема эпигенетических нарушений по мере прогрессии МДС с повышением числа генов с аберрантным метилированием, в частности, гена SFRP5.

Monosomal karyotype is the extremely poor variant of chromosomal aberrations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Retrospective analysis of 43 AML and 33 MDS patients was performed to determine typical clinical and hematological features of chromosomal karyotype. No characteristics typical for monosomal karyotype were found. Median of overall survival of AML and MDS patients was 6 and 8 months accordingly. At the same time some patients had relatively favorable course of their disease.

Monosomal karyotype is the extremely poor variant of chromosomal aberrations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Retrospective analysis of 43 AML and 33 MDS patients was performed to determine typical clinical and hematological features of chromosomal karyotype. No characteristics typical for monosomal karyotype were found. Median of overall survival of AML and MDS patients was 6 and 8 months accordingly. At the same time some patients had relatively favorable course of their disease.

Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected. It is concluded that the clinical course of secondary myeloid neoplasias is variable.

This rare type of acute leukemia, blast cells of which express myeloid and/or lymphoid markers, is mainly diagnosed using flow cytometric findings. The paper describes a clinical case of mixed-phenotype acute leukemia, in which B-cell lymphoid antigen expressions were revealed by a flow cytometric technique, while bone marrow morphological specimens showed the signs of myeloid differentiation specific to blast cells. It is concluded that there is a need for a comprehensive examination of patients with new-onset acute leukemia and for an aggregate analysis of flow cytometric results with morphological and cytochemical findings.

The efficacy of platelet transfusions that is mainly deter- mined by the immunological mechanisms still depends on the non-immunological factors causing the low platelet count increment after transfusions. The objective of the study was to identify clinical and hematological parameters that were associated with the efficacy of the platelet transfusions during induction chemotherapy according to 7+3 regimen in the patients with acute myeloid leukemias (AML) The data on 41 patients (median age: 42) were analyzed. The platelet transfusion was considered effica- cious when the 24-corrected platelet count increment was  4.5  10 9 /L. The patients were divided into 2 groups according to the efficacy  50 % or < 50 %, respectively. The groups showed no significant difference with respect to the age, AML variants according to the WHO classification and ELN prognostic scale, the response to chemotherapy, or the median of overall survival (OS). At the same time, the portion of the patients with the bone marrow (BM) blasts of myeloid origin (M1 and M2 variants of AML according to FAB classification) was greater in the group with the platelet transfusion efficacy of  50 %. In the group of < 50 % platelet transfusion efficacy, there was the greater portion of patients with BM blasts of monocytic origin (M4 and M5 variants according to FAB classification (p =.001). Also, the trend towards the decreased median of OS was noted in the patients with the pre-transfusion platelet count below 10  10 9 /L (p =0.049).