Ph阴性慢性骨髓增殖性肿瘤患者钙网质蛋白基因突变及其临床意义探讨

CALR mutation in patients with Ph negative chronic myeloproliferative neoplasms and its clinical significance

目的探究Ph阴性慢性骨髓增殖性肿瘤（myeloproliferative neoplasms，MPNs）患者钙网质蛋白（calreticulin，CALR）基因突变情况及其临床意义。方法对2012年1月至2015年1月于我院确诊的97例慢性骨髓增殖性肿瘤患者临床资料进行回顾性分析和随访，分析不同类型MPNs，包括真性红细胞增多症（polycythemia vera，PV）、原发性血小板增多症（essential thrombocythemia，ET）和原发性骨髓纤维化（primary myelofibrosis，PMF）患者的临床特点和基因突变情况，比较不同突变类型患者的血液学指标和预后（Cox回归模型）。结果在纳入的患者中，JAK2突变的发生率最高，为64.95%（63/97），其次为CALR突变19.59%（19/97）和三阴性10.31%（10/97），MPL突变的发生率最少为5.15%（5/97）。ET和PMF患者CALR突变发生率分别为28.57%（10/35）与28.13%（9/32），差异无统计学意义（χ^2＝1.616，P〉0.05）；PV患者未检出CALR基因突变。与JAK2突变患者相比，存在CALR突变患者的血红蛋白、白细胞和中性粒细胞水平较低（P〈0.05），存在CALR突变的ET患者血小板水平较低（P〈0.017），而存在CALR突变的PMF患者血小板水平较高（P〈0.017）。JAK2突变患者和CALR突变患者的疾病进展事件发生率分别为47.62%（30/63）和31.58%（6/19）（χ^2＝1.525，P〉0.05），CALR突变患者的疾病进展风险显著低于JAK2突变患者（HR＝0.46，95%CI 0.26～0.98，P〈0.05）。结论不同基因突变的MPNs患者临床特点间存在差异；CALR突变的MPNs患者的预后好于JAK2突变。

Objective To observe the CALR mutation in patients with Ph negative chronic myeloproliferative neoplasms（MPNs） and its clinical significance.Methods From January 2012 to January 2015, the clinical data of ninety-seven patients with chronic myeloproliferative neoplasms was retrospectively analyzed and followed up to analyze different types of MPNs, including the clinical characteristics and gene mutation of polycythemia vera（PV）, essential thrombocythemia（ET）and primary myelofibrosis （PMF）. The hematological parameters and prognosis of patients with different mutation types were compared （Cox regression model）.Results Among the patients, the incidence of JAK2 mutation was the highest, 64.95% （63/97）, followed by CALR mutation （19.59% （19/97）） and triple negative （10.31% （10/97））. The incidence of MPL mutation was 5.15% （5/97）, which was the lowest and CALR mutations in ET and PMF were 28.57% （10/35） and 28.13% （9/32）, respectively.The difference was not statistically significant （χ^2=1.616, P〉0.05）; the CALR gene mutation was not detected in PV patients.Compared with the JAK2 mutation, the hemoglobin, leukocyte and neutrophils in the patients with CALR mutation were lower （P〈0.05）, PLT levels were lower in CALR-mutant ET patients （P〈0.017）, whereas platelet levels in CALR-mutant PMF patients were higher （P〈0.017）. The incidence of disease progression in JAK2 and CALR mutation was 47.62% （30/63） and 31.58% （6/19） （χ^2=1.525, P〉0.05）. The risk of disease progression in patients with CALR mutation was significantly lower than that of JAK2 mutation （HR=0.46, 95%CI 0.26-0.98, P〈0.05）.Conclusion The clinical characteristics of MPNs patients with different gene mutations are different.The prognosis of MPNs patients with CALR mutation is better than that of JAK2 mutation.