Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations
Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2V617F, JAK2Ex12del, and MPLW515L/K mutations
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DOI：
10.1016/j.leukres.2015.11.002
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Inokuchi, Koiti
中科院分区：
文献类型：
--
作者：
Okabe, Masahiro;Yamaguchi, Hiroki;Inokuchi, Koiti
日本患者血栓形成并发真性红细胞增多症（PV）和原发性血小板增多症（ET）的风险明显低于西方人群，提示种族等遗传背景可能影响临床特征。本研究旨在阐明日本PV和ET患者基因突变、单倍型与临床特征之间的关系，对74例PV和303例ET患者的临床特征进行前瞻性评估。携带各种基因突变的PV患者之间没有临床差异，包括JAK2V617F等位基因负担。然而，与jak2v617f阳性ET患者和无突变的ET患者相比，CALR突变阳性ET患者的WBC计数、Hb值、Ht值和中性粒细胞碱性磷酸酶评分（NAP）显著降低，血小板显著增多。与正常对照相比，JAK2V617F、JAK2Ex12del或MAL突变患者中JAK246/1单倍型的频率显著更高，而在CALR突变阳性患者中没有发现显著差异。与jak2v617f阳性患者相比，CALR突变阳性患者的血栓发生率较低。我们的研究结果提示jak2v617f阳性ET患者和CALR突变阳性患者具有不同的ET发生机制和临床特征，提示未来可能需要进行治疗分层。(C) 2015 Elsevier Ltd.版权所有。
The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET.Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MAL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients.Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future. (C) 2015 Elsevier Ltd. All rights reserved.