JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan
JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan
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DOI：
10.1007/s12185-014-1567-1
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发表时间：
2014-05-01
影响因子：
2.1
通讯作者：
Komatsu, Norio
中科院分区：
文献类型：
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作者：
Edahiro, Yoko;Morishita, Soji;Komatsu, Norio
JAK2V617F是一种酪氨酸激酶JAK2的功能获得突变，在经典的骨髓增生性肿瘤(MPN)中经常被检测到。在本研究中，我们用交替结合的探针竞争-聚合酶链式反应检测了日本MPN患者的JAK2V617F等位基因负荷，这是我们小组最近开发的一种高定量方法。虽然我们观察到与JAK2V617F等位基因负荷相关的流行病学参数在我们的队列中与其他人群非常相似，但我们发现与以前的报道相比，日本真性红细胞增多症(PV)患者的JAK2V617F等位基因负荷更高，而日本MPN患者的血栓发生率更低。此外，尽管存在高红细胞计数，但一些携带JAK2V617F突变的患者没有被诊断为PV，因为他们的血红蛋白值低于WHO PV标准。在这些患者中，JAK2V617F等位基因的负荷与符合2008年WHO标准的PV患者惊人地相似，这表明这些患者可以被归类为PV。虽然确诊PV需要红细胞质量(RCM)的同位素测量，但我们的数据表明，在RCM尚未确定的情况下，精确测量JAK2V617F等位基因负荷可能会改善PV的诊断。
JAK2V617F, a gain-of-function mutation in the tyrosine kinase JAK2, is frequently detected in classical myeloproliferative neoplasms (MPNs). In the present study, we determined the JAK2V617F allele burden in Japanese MPN patients using alternately binding probe competitive-polymerase chain reaction, a highly quantitative method recently developed by our group. Although we observed strong similarities in terms of epidemiological parameters associated with the JAK2V617F allele burden between our cohort and others, we found a higher JAK2V617F allele burden in Japanese polycythemia vera (PV) patients and lower frequencies of thrombosis in Japanese MPN patients compared with previous reports. In addition, despite the presence of high red blood cell counts, some patients bearing the JAK2V617F mutation were not diagnosed as PV, as their hemoglobin values were lower than the WHO PV criterion. In these patients, the JAK2V617F allele burden was strikingly similar to that in PV patients fulfilling the 2008 WHO criteria, suggesting that these patients can be classified as PV. Although isotopic measurement of red cell mass (RCM) is required for definitive diagnosis of PV, our data suggest that precise measurement of the JAK2V617F allele burden may improve the diagnosis of PV when RCM has not been determined.