Takata Yuka, Seki Ritsuko, Kanajii Taisuke, Nohara Masayuki, Koteda Satoko, Kawaguchi Kuniki, Nomura Kei, Nakamura Takayuki, Morishige Satoshi, Oku Eijirou, Osaki Koichi, Hashiguchi Emichitoshi, Mouri Fumihiko, Yoshimoto Koji, Nagafuji Koji, Okamura Takashi
Department of Medicine, Kurume University School of Medicine.
Kurume Med J. 2014;60(3-4):89-97. doi: 10.2739/kurumemedj.ms63001. Epub 2014 May 26.
Thrombotic complications are a major cause of death in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which are closely associated with the JAK2 V617F activating mutation. However, whether the presence of the JAK2 V617F mutation affects thrombotic risk is currently unknown, although some reports have suggested a variable association with thrombosis. Therefore, we investigated the association between JAK2 V617F and various complications, including thrombosis, in Japanese patients with MPNs. We assessed the JAK2 V617F status in 140 patients who were diagnosed or doubted as having some type of MPN by utilizing a JAK2 V617F-specific guanine-quenching probe. JAK2 V617F was detected in 31 of 51 patients (60.8%) with essential thrombocythemia, all 16 patients (100%) with polycythemia vera, 4 of 11 patients (36.4%) with primary myelofibrosis, 2 of 18 patients (11.1%) with other types of MPNs, and none of the 44 patients with doubted MPN. In the 78 patients with classical MPN, JAK2 V617F correlated with a leukocyte count ≥10,000/μl (p=0.046). Complications of thrombosis, hemorrhage, and leukemic transformation occurred in 21 (41.2%), 4 (25.0%), and 3 (27.3%) patients with classical MPN, respectively, and thrombotic events (TE) occurred more frequently in patients with JAK2 V617F than without (p=0.047). Based on these findings, initial screening for the JAK2 mutation and careful monitoring for thrombotic events should be performed in patients with MPN.
血栓形成并发症是费城染色体阴性骨髓增殖性肿瘤（MPN）患者死亡的主要原因，这些肿瘤与JAK2 V617F激活突变密切相关。然而，尽管一些报告表明JAK2 V617F突变与血栓形成存在不同程度的关联，但目前尚不清楚该突变的存在是否会影响血栓形成风险。因此，我们调查了日本MPN患者中JAK2 V617F与包括血栓形成在内的各种并发症之间的关联。我们使用JAK2 V617F特异性鸟嘌呤淬灭探针评估了140例被诊断或怀疑患有某种类型MPN的患者的JAK2 V617F状态。在51例原发性血小板增多症患者中有31例（60.8%）检测到JAK2 V617F，16例真性红细胞增多症患者全部（100%）检测到，11例原发性骨髓纤维化患者中有4例（36.4%）检测到，18例其他类型MPN患者中有2例（11.1%）检测到，44例疑似MPN患者均未检测到。在78例典型MPN患者中，JAK2 V617F与白细胞计数≥10,000/μl相关（p = 0.046）。在典型MPN患者中，分别有21例（41.2%）、4例（25.0%）和3例（27.3%）发生了血栓形成、出血和白血病转化并发症，JAK2 V617F阳性患者的血栓形成事件（TE）发生率高于阴性患者（p = 0.047）。基于这些发现，应对MPN患者进行JAK2突变的初始筛查并密切监测血栓形成事件。
