骨髓增殖性疾病137例患者JAK2基因突变的研究

目的探讨信号分子JAK2基因突变——JAK2V617F在骨髓增殖性疾病（MPD）患者中的发生情况及诊断价值。方法采用等位基因特异性PCR方法及序列测定,检测137例MPD患者骨髓及外周血单个核细胞JAK2基因第12号外显子,研究JAK2V617F的发生情况,并结合细胞遗传学及分子生物学等检查结果分析其诊断价值。结果137例MPD患者共检出90例JAK2V617F阳性,总阳性率65．7％;其中真性红细胞增多症（PV）57例,阳性率73．7％（42／57）;原发性血小板增多症（ET）68例,阳性率58．8％（40／68）;特发性骨髓纤维化（IMF）12例,阳性率66．7％（8／12）;PV及ET患者突变型平均年龄高于野生型（P〈0．05）。115例进行过染色体检查,其中7例存在核型异常,突变型5例,阳性率为71．4％（5／7）;染色体核型正常者108例,突变型74例,阳性率68．5％;两组差异无统计学意义。结论MPD患者中JAK2V617F发生率较高,其发生与年龄相关,突变型平均年龄高于野生型。

The clinical implication of JAK2 mutation expression in patients with myeloproliferative disorders

OBJECTIVE: To investigate the frequency and clinical implication of JAK2V617F mutation in Chinese patients with myeloproliferative disorders (MPD). METHODS: Genomic DNA from bone marrow or blood mononuclear cells of 137 cases of MPD was screened with allele-specific polymerase chain reaction (PCR) and JAK2V617F mutation was detected with gel electrophoresis. There were 57 cases with polycythemia vera (PV), 68 with essential thrombocythemia (ET), 12 with idiopathic myelofibrosis (IMF). RESULT: JAK2V617F mutation was detected in 42 (73.7%) of the 57 patients with PV, 40 (58.8%) of the 68 with ET and 8 (66.7%) of the 12 with IMF. Sequence analysis of PCR products from selected patients confirmed the coexistence of both mutant and wild-type alleles. A higher prevalence was observed in elderly patients with MPD (P < 0.05). Cytogenetic analysis was performed in 115 of the 137 patients. Among the 108 patients with normal karyotype, JAK2V617F mutation was detected in 74 patients (68.5%) as compared with 5 of the 7 patients with karyotypic abnormalities (71.4%). CONCLUSION: JAK2V617F mutation occurs in a significant percentage of Chinese patients with the myeloproliferative disorders. There is a higher prevalence in elderly patients.