骨髓增殖性疾病中JAK2V617F基因突变及与临床特征的关系

摘要

This study was aimd to investigate the incidence of JAK2V617F mutation in BCR-ABL negative patients with myeloproliferative disorders ( MPD ) and its relation with clinical characteristics of MPD. The sensitive and specific test for JAK2V617F mutation was establishod for improving diagnosis level in Gansu province. 47 BCR/ABL negative MPD patients and 12 healthy people were enrolled in this study. Allele specific polymerase chain reaction ( ASPCR ) was used to amplify the exon 12 of JAK2 gene which harbours V617F mutation. The PCR products were identified by DNA sequencing. And its relation with clinical characteristics of MPD was analyzed also. The results indicated that the incidence of JAK2V617F positive mutation in 47 patients with BCR-ABL negative MPD was 74.5 ％(35/47), including 83.9 ％ ( 26/31 ) in patients with polycythemia vera (PV), 60 ％ (9/15 ) in patients with essential thrombocythemia (ET), only in one patient with idiopathic myelofibrosis (IMF). In PV group, the patients with JAK2V617F positive mutation had higher counts of WBC and Plt than patients with JAK2V617F negative mutation. In ET group, the patients with JAK2V617F positive mutation had higher WBC count and Hb level than those in the patients with JAK2V617F negative mutation with tendency of suffering from complications such as hepatosplenomegaly,haemorrhage and thrombosis. It is concluded that JAK2V617F mutation is more frequent in BCR-ABL negative patients with MPD, the AS-PCR method is sensitive and specific for detection of the mutation and may successfully use in clinical examination.%本研究旨在检测JAK2V617F基因突变在BCR-ABL阴性的骨髓增殖性疾病(myeloproliferative disorder,WPD)患者中的发生率,探讨其与MPD患者临床特征间的关系,建立敏感特异的JAK2V617F基因点突变的临床检测方法,提高骨髓增殖性疾病的临床诊断水平.选择兰州大学第一医院确诊的47例BCR-ABL阴性的MPD患者及12例健康正常人,抽提外周血细胞全血DNA,采用等位墓因特异性聚合酶链反应(AS-PCR)技术检测各组JAK2V617F基因突变情况及突变基因序列,并结合临床资料作进一步分析.结果表明,BCR-ABL阴性的MPD患者JAK2V617F基因突变阳性率为74.5%(35/47),其中真性红细胞增多症(PV)阳性突变率为83.9 %(26/31),原发性血小板增多症(ET)阳性突变率为60%(9/15),特发性骨髓纤维化(IMF)阳性患者只有1例.突变阳性的PV患者白细胞和血小板计数较突变阴性者高,突变阳性的ET患者白细胞计数和血红蛋白含量较突变阴性者高,且突变阳性的ET患者更易发生肝脾种大、出血、血栓形成等并发症.结论:JAK V617F突变在BCR-ABL阴性的MPD患者中有较高的检出率,AS-PCR技术对该突变有较好的敏感特异性,可以成功地应用于临床检测.