骨髓增殖性疾病JAK2V617F点突变研究

Tyrosine Kinase JAK2V617F Mutation in Human Myeloproliferative Disorders

本研究旨在对bcr/abl融合基因阴性的骨髓增殖性疾病(MPD)病人进行JAK2V617F点突变检测,探讨该突变在此类病人中的发生率和临床意义。采用逆转录聚合酶链反应(RT-PCR)检测70例典型MPD病人bcr/abl融合基因,用等位基因特异性聚合酶链反应(AS-PCR)检测样本JAK2V617F点突变,对有突变的病例进行测序验证。结果表明,慢性髓系白血病(CML)病人bcr/abl融合基因均为阳性,JAK2V617F突变为阴性;余bcr/abl融合基因均为阴性,JAK2V617F阳性率在真性红细胞增多症(PV)病人为75%,在原发性血小板增多症(ET)病人为30%,在特发性骨髓纤维化(IMF)病人为50%。JAK2V617F在CML和bcr/abl阴性MPD病人中的分布有显著性差异(p<0.05)。结论:JAK2V617F可能为真性红细胞增多症、原发性血小板增多症、特发性骨髓纤维化的特征性分子事件,可作为一个独立的分子指标用于此三类疾病的临床诊断。

This study was aimed to investigate the JAK2V617F mutation in myeloproliferative disorders（MPD） and to evaluate the significance of JAK2V617F in diagnosis and therapy of MPD. The bcr/abl fusion gene in 70 MPD patients was detected by reverse transcription polymerase chain reaction （PT-PCR）. The JAK2V617F mutation was detected by allele-specific polymerase chain reaction（AS-PCR） and the results were confirmed by sequence analysis. The results indicated that the bcr/abl fusion gene could be detected in 38 patients with chronic myeloid leukemia（ CML）, but not in the 32 none-CML patients. The JAK2V617F mutation was detected in 12 out of 16 （ 75% ） patients with polycythemia vera （ PV ）, 3 out of 10 （ 30% ） patients with essential thrombocythemia （ ET）, 3 out of 6 （ 50 % ） patients with idiopathic myelofibrosis（ IMF）, but not in any of the CML patients. The JAK2V617F mutation frequencies between CML and bcr/abl negative MPD patients were statistically significant（p 〈 0.05 ）. It is concluded that the JAK2V617F may be a characteristic molecular event in PV, ET and IMF patients which may serve as an important molecular marker for the diagnosis and classification of the three diseases.