BCR-ABL阴性的骨髓增殖性肿瘤JAK2基因V617F突变分析

Relationship between JAK2 gene V617F mutation and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms

目的:探讨BCR-ABL阴性的骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者蛋白质酪氨酸激酶基因(JAK2)V617F突变的发生率及其与患者临床特征的关系。方法:抽提65例MPN患者骨髓细胞DNA(其中真性红细胞增多症28例,特发性血小板增多症30例,特发性骨髓纤维化7例),应用等位基因特异性PCR技术(allelespecific PCR,AS-PCR)分析JAK2基因V617F突变的发生率,并分析此突变与外周血细胞计数及血栓发生率等临床特征的关系。结果:65例MPN患者的V617F突变阳性率为64.62%(42/65)。其中真性红细胞增多症患者的阳性率为75.00%(21/28),其白细胞及血小板计数较非突变者均显著增高(P<0.001);特发性血小板增多症患者该突变的阳性率为56.67%(17/30),其白细胞计数和血红蛋白水平均较非突变者显著增高(P<0.05);而7例特发性骨髓纤维化患者中4例被检出此突变阳性,其白细胞、血小板计数及血红蛋白水平与非突变者比较,差异则无统计学意义。同时,携带V617F突变的MPN患者血栓发生率明显高于非突变者(P<0.05)。结论:JAK2基因V617F突变是我国BCR-ABL阴性MPN患者主要的分子遗传标志,可作为临床诊断的指标之一,而此突变对临床特征有一定影响。

Objective： To investigate the relationship between V617F mutation in JAK2 gene and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms （MPN）. Methods： Sixty-five patients with MPN, including 28 subjects with polycythemia vera （PV）, 30 subjects with essential thrombocythemia （ET） and 7 subjects with idiopathic myelofibrosis （IMF） were enrolled in this study. Bone marrow cell DNA was extracted from MPN patients, and V617F mutation in JAK2 gene was identified by allele specific PCR （AS-PCR）. The correlation between V617F mutation and clinical characteristics such as peripheral blood cell count and incidence of thrombosis were analyzed. Results： Of the 65 patients, 42 subjects harbored V617F mutation （64.62%）. The positive rates of V617F mutation in PV and ET patients were 75.00% （21 subjects） and 56.67% （17 subjects）, respectively. Four of the 7 patients with IMF were V617F mutation positive. For PV patients, the levels of white blood cell count and platelet count in V617F mutation carriers were significantly higher than that in non-carriers （P〈0.05）. For ET patients, the levels of white blood cell count and hemoglobin in V617F mutation carriers were significantly higher than that in non-carriers （P〈0.05）. For IMF patients, however, no significant differences were found between mutation carriers and non-carriers. The incidence of thrombosis in V617F mutation carriers was higher than that in non-carriers （P〈0.001）. Conclusions： V617F mutation in JAK2 is a major molecular genetic marker for Chinese patients with BCR-ABL-negative myeloproliferative neoplasms. This mutation has impacts on clinical characteristics and can be used as a criterion for the diagnosis of BCR-ABL-negative myeloproliferative neoplasm.