Introduction. The pathogenesis of myeloproliferative neoplasms is associated with the chimeric gene BCR-ABL1 or with one of the driver mutations in the genes JAK2, MPL and CALR (Calreticulin). However, the classifi cation of the World Health Organization lists no myeloid neoplasms with more than one driver genetic abnormality. Aim. To search for mutations in the genes JAK2, MPL and CALR in patients with BCR-ABL1-positive chronic myeloid leukemia (CML), as well as to evaluate the kinetics of the discovered mutations during tyrosine kinase inhibitor (TKI) therapy. Materials and methods. mRNA and DNA samples isolated from blood and bone marrow cells of 567 CML patients, who underwent periodic monitoring of the BCR-ABL1 transcript level over the 2012–2019 period were included in the study The BCR-ABL1 transcript level was determined using a highly sensitive quantitative real-time polymerase chain reaction. The mutations JAK2V617F and MPLW515L/K were detected using real-time quantitative allele-specifi c polymerase chain reaction. Mutations in the CALR gene were investigated using fragment analysis followed by Sanger sequencing. Results. The combination of the BCR-ABL1, JAK2 and CALR gene mutations among CML patients receiving TKIs was 1.23 % (7/567). Out of these, the combination of BCR-ABL1 with JAK2V617F and the combination of BCR-ABL1 with CALR gene mutations were detected in 0.88 % (5/567) and 0.35 % (2/567) of cases, respectively. During TKI therapy, in 5 out of 7 patients, the level of BCR-ABL1 reached major molecular response (MR). In 4 of these patients, the therapy was discontinued. These patients are currently in molecular remission. In the remaining 2 patients, major MR was not achieved, despite the use of second-generation TKI preparations. Conclusions. The combination of the BCR-ABL1 chimeric gene with gene mutations Jak2 or CALR was a rare event and amounted to 0.88 and 0.35 % of cases, respectively. The combination of BCR-ABL1 with Jak2V617F and CALR mutations does not always impede the achievement of major MR.

A small number of patients showed simultaneous occurrence of both JAK2(V617F) mutation and BCR/ABL translocation. The problem is whether this simultaneous occurrence of molecular markers indicates the presence of two diseases Ph-negative myeloproliferative disease and Ph-positive myeloproliferative disease. We present two cases of simultaneous occurrence of both JAK2(V617F) mutation and BCR/ABL p210 translocation. Reduction of the BCR-ABL p210 transcript level to 0.29 and 0.014% in cases 1 and 2, respectively, was paralleled by increase of JAK2V617F level to 100% in the former case and its reduction to 5% and subsequent increase to 43% in the latter case.

ФГБУ «Гематологический научный центр» Минздрава России, Но

Time course of hepatitis B and C virus infection in patients with hematological disorders. T. Ts. Garmaeva, S. M. Kulikov, E. A. Mikhailova, R. E. Igla, T. F. Shmatova, E. G. Gemdzhyan, L. O; Grumbkova, N. G. Yaroslavtseva, A. V. Somova, T. A. Tupoleva, T. V. Makarik, O. A. Glinshchikova, I. S. Fevraleva, A. B. Sudarikov, F. P. Filatov, V. G. Savchenko. Hematology Research Center, Moscow. The patients with hematological disorders refer to a population of a high risk of hepatitis B and C virus infection. The risk factors in these patients are repeated blood transfusions and medical manipulations involving violation of the skin intactness. We carried out a dynamic analysis of hepatitis B and C virus infection in hematological patients during hospitalization and studied the risk of nosocomial infection factors. We found out high infection rates: the incidence of hepatitis B increased 3.5 times (from 14.7 to 51%), incidence of hepatitis C increased 2.7 times (from 7 to 19%), and of coinfection 7-fold (from 2 to 14%). Blood component transfusions were the leading risk factor for nosocomial hepatitis B and C virus infection. Medical manipulations were the second risk factor for hepatitis B virus infection.

Clinical epidemiological characteristics of the incidence of infection by hepatites B and C viruses in hematological patients on admission to hospital. T. Ts. Garmaeva, S. M. Kulikov, E. A. Mikhailova, T. F. Shmatova, E. G. Gemjyan, T. A. Tupoleva, L. O. Grumbkova, N. G. Yaroslavtseva, A. V. Somova, T. V. Makarik, O. A. Glinshchikova, I. S. Fevraleva, A. B. Sudarikov, F. P. Filatov, V. G. Savchenko. Hematology Research Center, Moscow. The incidence of infection by viruses of hepatitis B (HBV) and hepatitis C (HCV) in different population groups is determined by the main factors of viral infection transmission risk in these groups. The aim of this study was clinical and epidemiological characterization of hematological patients, specifically, evaluation of the probability of detection of HBV and HCV markers (in connection with the risk factors) on admission to hospital. The incidence of HBV and HCV infections in hematological patients on admission to hospital was at least 2-fold higher than in the population of Russia. The main significant factors of viral infection risk in hematological patients were history of blood transfusions and medical manipulations, as well as contacts with patients with viral hepatitis B and hepatitis C, and a history of invasive studies. The impact of such well-known risk factors as narcotic abuse and active sexual behavior is extremely negligible in hematological patients. The importance of detecting nonspecific indicators of HBV and HCV infection, hepatic enzymes, and total bilirubin values, improving the detection of potentially infected individuals and donors of blood components, is confirmed.

Hepatites B (HBV), C (HCV) viruses, and parvovirus B19 (PV B19) are particularly hazardous for patients receiving multiple transfusions of blood components during treatment, as donor blood testing for serological markers of viral hepatites alone does not completely rule out the probability of infection, and no testing for PV B19 is carried out. We suggest a diagnostic system based on multiplex chain reaction in the real time mode for simultaneous testing of blood serum and plasma specimens and tissue biopsy specimens for HBV, HCV, and PV B19. A total of 737 patients blood specimens were tested by this multiplex method; HBV was detected in 45 patients, HCV in 113, PV B19 in 25 patients; HBV + HCV were detected in 4 patients, PV B19 + HCV in 1 patient. Our system for complex monitoring of HBV, HCV, and PV B19 will timely detect the infection or will clear out the cause of clinically diagnosed hepatitis.

Pilot results are presented of a prospective study on monitoring of risk factors and indicators of HBV and HCV infection in hematological patients. This study was conducted because hepatitis viruses infection is highly prevalent in donor population, blood components, massive transfusion load in hematological patients and, therefore, high risk of posttransfusion infection with HBV and HCV. Viral infection of the liver reduces tolerance of intensive treatment and chances for long-term survival.

nterspecies difference in humans by HPA antigens favours patient alloimmunization in blood component transfusion therapy, firstly in thrombocyte transfusions, and development of different pathological conditions. Aim of the work was study of distribution of HPA genes in blood donors in Moscow city for determination of minimal contingent of HPA typed donors for providing with transfusions of patients in one hematology clinics. HPA genotyping has been carried out by polymerase chain reaction using DNA from 100 sibling donors (SD) and 197 regular donors (RD) of blood components from Blood Bank of Hematological Research Center (Moscow). SD were typed by HPA-1-6w genes, and RD were typed by HPA-1 -5 allelic genes. The obtained data on rate of HPA alleles and genotypes in donors from Moscow city appeared to be comparable to rates of the genes in East European population. An increased rate of HPA-2b gene (23.6%) comparing to its mean rate in white race individuals (13.2%) was revealed as a distinctive marker. Using data on rates of genotypes in test group of donors necessary contingent of HPA typed donors has been calculated. Its value appeared to be 1500-2000 donors. Under this condition it will be 90% possibility for forming of HPA-matched donor group sufficient for prolonged transfusion therapy.