Significance of the XRCC1 gene Arg399Gln polymorphism in the pathogenesis of the chronic myeloproliferative diseases

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.We investigated the association between Arg399Gln polymorphism in DNA repair gene XRCC1 and chronic myeloproliferative diseases. 79 patients with chronic myeloid leukemia (CML), 91 patient with polycythemia vera (PV), 132 patients with essential thrombocythemia (ET). 50 patients with myelofibrosis and 114 controls were included in the study. We genotyped the polymorphism in XRCC1 gene by using polymerase chain reaction in real-time with TaqMan assay. The detection and quantification of the JAK2 gene V617F mutation allele burden was carried out by means of "Pyromark q24" pyrosequencing. The presence of at least one XRCC1 399Gln allele was found to be significantly different in patients with CML (OR 1.53; 95% CI 0.67-3.51) and ET (OR 1.31; 95% CI 0.61-2.78) in comparison with controls. The presence of XRCC1 399Gln allele was associated with the resistance to imatinib. We found no interactions between the XRCC1 genotype and the level JAK2 allelic burden. These data suggest about a significance of the XRCC1 gene product in the control of precursor cells of the myeloid differentiation in CML and ET cells. Testing Arg399Gln polymorphism in XRCC1 gene may be useful for the assessment of the prognosis and treatment efficacy

Significance of the XRCC1 gene Arg399Gln polymorphism in the pathogenesis of the chronic myeloproliferative diseases

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.We investigated the association between Arg399Gln polymorphism in DNA repair gene XRCC1 and chronic myeloproliferative diseases. 79 patients with chronic myeloid leukemia (CML), 91 patient with polycythemia vera (PV), 132 patients with essential thrombocythemia (ET). 50 patients with myelofibrosis and 114 controls were included in the study. We genotyped the polymorphism in XRCC1 gene by using polymerase chain reaction in real-time with TaqMan assay. The detection and quantification of the JAK2 gene V617F mutation allele burden was carried out by means of "Pyromark q24" pyrosequencing. The presence of at least one XRCC1 399Gln allele was found to be significantly different in patients with CML (OR 1.53; 95% CI 0.67-3.51) and ET (OR 1.31; 95% CI 0.61-2.78) in comparison with controls. The presence of XRCC1 399Gln allele was associated with the resistance to imatinib. We found no interactions between the XRCC1 genotype and the level JAK2 allelic burden. These data suggest about a significance of the XRCC1 gene product in the control of precursor cells of the myeloid differentiation in CML and ET cells. Testing Arg399Gln polymorphism in XRCC1 gene may be useful for the assessment of the prognosis and treatment efficacy

The identifiability of patients with carcinogenic somatic mutation of Junus kinase-2 (V617FJAK2) within the framework of programs of dispensary and preventive examinations

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The article presents results of identification of somatic mutation in in gene Junus kinase-2 (V617F JAK2) in blood samples of persons included in program of dispensarization of adult population and periodic preventive examinations of workers of railroad transport. The technology of allele-specific polymerase chain reaction in real-time in pooled trials from blood samples received by clinical diagnostic laboratory for hematological analysis was developed with purpose of carrying out study. The results of testing among 986persons aged from 45 to 90 years (median - 69 years) permitted to establish 0.7% of patients (3 females and 4 males) with mutation V617F JAK2. The high thrombogenic potential of mutation V617F JAK2 and its involvement into pathogenesis of chronic myeloid tumors makes appropriate to include test on its detection into menu of laboratory analyses of program of dispensarization of population

The identifiability of patients with carcinogenic somatic mutation of Junus kinase-2 (V617FJAK2) within the framework of programs of dispensary and preventive examinations

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The article presents results of identification of somatic mutation in in gene Junus kinase-2 (V617F JAK2) in blood samples of persons included in program of dispensarization of adult population and periodic preventive examinations of workers of railroad transport. The technology of allele-specific polymerase chain reaction in real-time in pooled trials from blood samples received by clinical diagnostic laboratory for hematological analysis was developed with purpose of carrying out study. The results of testing among 986persons aged from 45 to 90 years (median - 69 years) permitted to establish 0.7% of patients (3 females and 4 males) with mutation V617F JAK2. The high thrombogenic potential of mutation V617F JAK2 and its involvement into pathogenesis of chronic myeloid tumors makes appropriate to include test on its detection into menu of laboratory analyses of program of dispensarization of population

JAK2V617F-positive clonal hematopoiesis of indeterminate potential in pregnant women

Aim: to assess the prevalence of V617F somatic mutation of the JAK2 gene in pregnant women.Materials and methods. This non-interventional study was performed in the framework of routine clinical practice and included 1532 samples of venous blood from pregnant women who applied for medical assistance at Krasnoyarsk Regional Clinical Center for Maternal and Child Welfare. We used blood samples left after all routine laboratory tests had been done. These leftovers were pooled in the way that ensured an equal ratio of nucleated cells. Each pool contained 7 separate blood samples. The unused samples that remained after the pooling were frozen and stored at –20°C until the end of entire testing procedure. The V617F JAK2 mutation was detected by the real-time allele-specific polymerase chain reaction test.Results. Among the examined pregnant women, 6 (0.4 %) were identified as carriers of V617F JAK2 mutation. Three women with this mutation suffered from infertility for 4, 5, and 10 years; two of them had repeated miscarriages in the first trimester of pregnancy. The 6 women – carriers of this mutations had no concomitant genetic polymorphisms typical of thrombophilia (factors FII, FV), and no abnormal coagulation characteristics. Analysis of their medical records showed that in the past, two of these women had gestational hypertension, one developed a clinical picture of preeclampsia, and another one (with the maximum presence of the mutant allele) had a history of acute lymphoblastic leukemia followed by stable remission.Conclusion. The routine laboratory detection of the V617F JAK2 mutation can facilitate timely identification of the increased risk of pregnancy pathology, as well as timely diagnosis of hematological cancer