急性髓系白血病患者表观遗传学修饰基因突变的分析

Analysis of epigenetic modification gene mutations among patients with acute myeloid leukemia

目的探讨急性髓系白血病(AML)患者表观遗传学修饰基因突变(EMMs)的携带率及其临床特征。方法选取2011年5月至2021年2月于连云港市第一人民医院初诊的172例AML患者为研究对象。应用二代测序技术检测42种髓系基因的变异情况,回顾性分析EMMs患者的临床及分子学特征,以及去甲基药物(HMAs)对其生存的影响。结果在172例初诊的AML患者中,71例(41.28%)携带EMMs[EMMs(+)],变异基因分别为TET2(14.53%,25/172)、DNMT3A(11.63%,20/172)、ASXL1(9.30%,16/172)、IDH2(9.30%,16/172)、IDH1(8.14%,14/172)、EZH2(0.58%,1/172)。EMMs(+)患者的外周血血红蛋白低于EMMs(-)患者(72 g/L vs.88 g/L,Z=-1.985,P<0.05)。老年AML患者的EMMs(+)携带率显著高于青年患者[71.11%(32/45)vs.30.70%(39/127),χ^(2)=22.38,P<0.001]。EMMs与NPM1基因变异呈正相关(r=0.413,P<0.001),与CEPBA基因双变异呈负相关(r=-0.219,P<0.05)。EMMs(+)的预后中危AML患者中,与常规化疗方案相比,含HMAs的化疗方案可以延长患者中位无进展生存时间(PFS)及中位总生存时间(OS)(PFS:11.5个月vs.25.5个月,P<0.05;OS:12.5个月vs.27个月,P<0.05)。在老年患者中,与常规方案相比,含HMAs化疗方案也可延长中位PFS及中位OS(PFS:4个月vs.18.5个月,P<0.05;7个月vs.23.5个月,P<0.05)。结论AML患者的EMMs携带率较高,含HMAs的化疗方案可以延长预后中危及老年AML患者的生存,对AML的个体化治疗有一定的指导意义。

Objective To investigate the carrier rate and clinical characteristics of epigenetic modification gene mutations(EMMs)among patients with acute myeloid leukemia(AML).Methods One hundred seventy two patients who were initially diagnosed with AML at the First People′s Hospital of Lianyungang from May 2011 to February 2021 were selected as the study subjects.Next-generation sequencing was carried out to detect variants of 42 myeloid genes among these patients.Clinical and molecular characteristics of patients with EMMs and the effect of demethylation drugs(HMAs)on their survival were analyzed.Results Among the 172 AML patients,71(41.28%)were found to harbor the EMMs,and carrier rates were TET2(14.53%,25/172),DNMT3A(11.63%,20/172),ASXL1(9.30%,16/172),IDH2(9.30%,16/172),IDH1(8.14%,14/172),EZH2(0.58%,1/172).Patients with EMMs(+)had lower peripheral hemoglobin compared with those with EMMs(-)(72 g/L vs.88 g/L,Z=-1.985,P<0.05).The proportion of EMMs(+)among elderly AML patients was significantly higher than that of young AML patients[71.11%(32/45)vs.30.70%(39/127),χ^(2)=22.38,P<0.001].EMMs(+)were significantly correlated with NPM1 gene variants(r=0.413,P<0.001),while negatively correlated with CEPBA double variants(r=-0.219,P<0.05).Compared with conventional chemotherapy regimens,HMAs-containing chemotherapy regimens have improved the median progression-free survival(PFS)and median overall survival(OS)among intermediate-risk AML patients with EMMs(+)(PFS:11.5 months vs.25.5 months,P<0.05;12.5 months vs.27 months,P<0.05).Similarly,Compared with conventional chemotherapy regimens,chemotherapy with HMAs had increased median PFS and median OS in elderly AML patients with EMMs(+)(4 months vs.18.5 months,P<0.05;7 months vs.23.5 months,P<0.05).Conclusion Patients with AML have a high rate of EMMs carriage,and HMAs-containing chemotherapy regimens can prolong the survival of elderly patients with AML with poor prognosis,which may provide a reference for individualized treatment.