老年急性髓系白血病基因突变及临床意义

Mutation and its clinical significance of acute myeloid leukemia in elderly patients

目的:探讨老年急性髓系白血病(AML)患者基因突变情况及其临床意义。方法:采用二代测序方法检测69例初诊老年AML患者基因突变情况,包括TET2,DNMT3A,NPM1,CEBPα,EZH2,JAK2,U2AF1,RUNX1,NRAS,TP53,IDH2,C-KIT,SRSF2,SF3B1,ASXL1,FLT3,ETV6,PHF6,CBL,SETBP1,ZRSR2,收集患者临床资料,分析突变发生率及临床意义,针对49例接受DCAG治疗患者分析疗效及预后。结果:老年AML患者基因突变频率高,突变率为94.2%(65/69),NPM1,SRSF2,SF3B1在4种白血病分型间分布存在差异(均P<0.05)。C-KIT突变易出现在染色体核型低中危组(P<0.001),TP53突变与高危核型有关(P=0.003)。TP53突变,ETV6突变,合并症数目,染色体核型及DCAG首次诱导完全缓解均为影响预后的因素,其中TP53突变,首次诱导完全缓解及合并症数目为独立危险因素(P<0.05)。结论:老年AML患者基因突变及细胞遗传学异常对临床诊疗工作具有重要意义。

Objective：To investigate the mutations and clinical significance of genes in elderly patients with acute myeloid leukemia（AML）.Method：Next-generation sequencing was used to detect newly diagnosed elderly AML patients,including TET2,DNMT3 A,NPM1,CEBPα,EZH2,JAK2,U2 AF1,RUNX1,NRAS,TP53,IDH2,C-KIT,SRSF2,SF3 B1,ASXL1,FLT3,ETV6,PHF6,CBL,SETBP1,ZRSR2.We collected the clinical data and analyzed the incidence as well as clinical significance.The efficacy and prognosis of 49 patients treated with DCAG were analyzed.Result：The prevalence of the selected mutations was 94.2%（65/69）in elderly patients with AML,and the distribution of NPM1,SRSF2 and SF3 B1 were different among 4 leukemia types（P〈0.05）.C-KIT mutations were found in the group with low-risk chromosome karyotype（P〈0.001）and TP53 mutations were associated with poor-risk group chromosome karyotype（P=0.003）.TP53 mutation,ETV6 mutation,the number of complications,chromosome karyotype and achievement of complete remission after DCAG first induction were the prognostic factors,whereas TP53 mutation,achievement of complete remission after the first induction and complications were independent risk factors（P〈0.05）.Conclusion：Gene mutation and cytogenetic abnormalities in elderly patients with AML have great significance to clinical diagnosis and treatment.