Mishcheniuk O Y, Kostukevich O M, Dmytrenko I V, Sholoyko V V, Prokopenko I M, Martina Z V, Pilipenko G V, Klymenko S V
State Institution "National Research Center for Radiation Medicine" of the National Academy of Medical Sciences of Ukraine, Kyiv 04050, Ukraine.
Exp Oncol. 2013 Sep;35(3):202-6.
The aim of this study was to examine the JAK2 V617F, the G1691A allele of factor V, and the G20210A prothrombin gene mutation status, and their predictive value for thrombosis in patients with Ph-negative myeloproliferative neoplasms (MPN) in Ukraine, with special emphasize to patient exposed to ionizing radiation due to the Chernobyl accident.
There were 198 patients with Ph-negative MPN included in the study. Of these, 45 patients had experienced radiation exposure due to the Chernobyl accident. The JAK2 V617F mutation, the G1691A of factor V and the G20210A of prothrombin were detected by allele-specific polymerase chain reaction.
The polycythemia vera and essential thrombocythemia patients in unexposed group and Chernobyl patients were comparable in terms of the JAK2 V617F mutation prevalence with the frequency of anomaly corresponding well to the published data on unselected cases of these types of Ph-negative MPN. The JAK2 V617F mutation was less common on the border of statistical significance (p = 0.08) in Chernobyl primary myelofibrosis (PMF) patients than in non-exposed patients. JAK2 V617F positive patients had higher level of leukocytes (p = 0.03), hemoglobin (p =0.04) and splenomegaly (p = 0.04) than those without mutation. The JAK2 V617F mutation was strong predictor for thrombosis in essential thrombocytemia patients (relative risk=3.1, 95% CI = 1.7-16.4, p = 0.03). In PMF, the association with thrombosis was found for the G1691A allele of factor V (p = 0.03). The risk of thrombosis associated with the inherited thrombophilia in PMF patients was 7.0-fold (95% CI = 1.41-33.1, p = 0.03) higher than in polycythemia vera patients. The inherited thrombophilia increased risk of thrombotic complication 5.4-fold (95% CI = 1.41-18.17, p = 0.01) in overall cohort of Ph-negative myeloproliferative neoplasms patients. This trend continued in Chernobyl patients (p = 0.02), but not in unexposed cases.
Our findings confirm previous results of other studies reporting that the JAK2 V617F mutation significantly and independently influences on a disease phenotype in Ph-negative MPN. The inherited thrombophilia is important risk factors of the thrombosis development in overall cohort primary myelofibrosis patients, and especially in disease developed following radiation exposure.
本研究旨在检测JAK2 V617F、凝血因子V的G1691A等位基因以及凝血酶原基因G20210A突变状态，并评估其对乌克兰Ph阴性骨髓增殖性肿瘤（MPN）患者血栓形成的预测价值，特别关注因切尔诺贝利事故暴露于电离辐射的患者。
本研究纳入198例Ph阴性MPN患者。其中，45例患者因切尔诺贝利事故遭受辐射暴露。采用等位基因特异性聚合酶链反应检测JAK2 V617F突变、凝血因子V的G1691A以及凝血酶原的G20210A。
未暴露组的真性红细胞增多症和原发性血小板增多症患者以及切尔诺贝利事故患者在JAK2 V617F突变患病率方面具有可比性，异常频率与已发表的这些类型Ph阴性MPN未选择病例的数据相符。切尔诺贝利原发性骨髓纤维化（PMF）患者中JAK2 V617F突变在统计学意义临界值上（p = 0.08）比未暴露患者少见。JAK2 V617F阳性患者的白细胞水平（p = 0.03）、血红蛋白水平（p = 0.04）和脾肿大（p = 0.04）均高于未突变患者。JAK2 V617F突变是原发性血小板增多症患者血栓形成的强预测因子（相对风险=3.1，95%可信区间=1.7 - 16.4，p = 0.03）。在PMF中，发现凝血因子V的G1691A等位基因与血栓形成有关（p = 0.03）。PMF患者中与遗传性血栓形成倾向相关的血栓形成风险比真性红细胞增多症患者高7.0倍（95%可信区间=1.41 - 33.1，p = 0.03）。在Ph阴性骨髓增殖性肿瘤患者的总体队列中，遗传性血栓形成倾向使血栓并发症风险增加5.4倍（95%可信区间=1.41 - 18.17，p = 0.01）。这种趋势在切尔诺贝利事故患者中持续存在（p = 0.02），但在未暴露患者中未出现。
我们的研究结果证实了其他研究先前的结果，即JAK2 V617F突变对Ph阴性MPN的疾病表型有显著且独立的影响。遗传性血栓形成倾向是总体队列原发性骨髓纤维化患者血栓形成发展的重要危险因素，尤其是在辐射暴露后发生的疾病中。
