中国成人急性髓系白血病遗传分子学特征及预后分析

Molecular genetics characterization and prognostic analysis of adult acute myeloid leukemia in China

目的:探讨急性髓系白血病(AML)遗传分子学特征及预后影响因素。方法:回顾分析160例初诊AML患者的临床资料,采用常规G显带技术进行染色体核型分析,实时荧光定量聚合酶链式反应法(PCR)检测融合基因,DNA测序技术检测基因突变情况,采用COX回归分析及Kaplan-Meier生存曲线分析影响患者总生存期(OS)的可能因素。结果:160例AML患者中,染色体核型异常者74例(46.2%),复杂核型15例(9.4%),单体核型18例(11.3%);160例患者突变频率排名前五的基因依次为WT1(22.5%),NPM1(16.9%),DNMT3A(16.9%),CEBPA(15.0%),FLT3-ITD(15.0%);DNMT3A、FLT3、IDH2、RUNX1基因突变者相比于未突变者生存期缩短(P<0.05),CEBPA基因突变者相比于未突变者生存期延长(P<0.05);多因素结果分析显示初次诱导未达CR、未行移植、预后不良组、伴DNMT3A突变、伴FLT3突变是AML患者OS的独立不良预后因素。结论:160例AML患者染色体异常及基因突变较常见,AML预后与患者遗传分子学特征、治疗反应及是否移植等相关。

Objective:To investigate the molecular genetics characterization and prognostic factors of acute myeloid leukemia(AML).Methods:We retrospectively analyzed the clinical data of 160 newly diagnosed AML patients,and used conventional G-banding technique for chromosomal karyotypes.Real-time fluorescence quantitative polymerase chain reaction(PCR)was used to detect fusion genes,and DNA sequencing was used to detect mutations,and COX regression analysis and Kaplan-Meier survival curve were used to analyze the probable factors influencing the overall survival(OS)of the patients.Results:Among 160 AML patients,74 patients(46.2%)had abnormal chromosomal karyotypes,15 patients(9.4%)had complex karyotypes,and 18 patients(11.3%)had monosomal karyotypes.The top five genes with the highest mutation frequencies among the 160 patients were,in order,WT1(22.5%),NPM1(16.9%),DNMT3A(16.9%),CEBPA(15.0%),and FLT3-ITD(15.0%).Those with mutations in DNMT3A,FLT3,IDH2,and RUNX1 genes had a shorter survival compared to those with no DNMT3A,FLT3,IDH2,and RUNX1 mutation(P<0.05),and those with CEBPA gene mutations had prolonged survival compared to those without CEBPA mutations(P<0.05).Multivariate regression analysis showed that failure to reach CR after initial induction,no transplantation,adverse prognostic group,with DNMT3A mutation,and with FLT3 mutation were independent poor prognostic factors for OS in AML patients.Conclusion:Chromosomal abnormalities and gene mutations were common in 160 AML patients,and the prognosis was related to molecular genetics characterization,treatment response and transplantation.