急性髓系白血病患者134例的基因变异特点

Characteristics of genetic variants in 134 patients with acute myeloid leukemia

目的探讨134例初诊急性髓系白血病(AML)患者的基因变异特点。方法回顾性分析2017年6月至2022年6月在联勤保障部队第九四〇医院初诊为AML(非急性早幼粒细胞白血病)134例患者的临床资料。基于二代测序进行AML相关基因检测,研究分析AML患者的变异频率及变异特点。本研究采用SPSS v26.0软件进行统计学处理,用似然比χ^(2)检验和Fisher确切率法检验进行数据分析。结果134例患者中,男72例,女62例,男女比例为1.7:1,中位年龄51岁(9~86岁)。120例(76.1%)患者发生基因变异,26例(19.4%)患者为单基因变异,27例(20.1%)患者存在2个基因变异,49例(36.6%)患者同时携带≥3个基因变异;32例(23.9%)患者未检测到任何基因变异。134例患者总变异检出率在10%以上的变异基因依次为NPM1(n=24,17.91%)、FLT3-ITD(n=21,15.67%)、DNMT3A(n=20,14.93%)、CEBPA单变异(n=14,10.45%)、TET2(n=14,10.45%)、NRAS(n=14,10.45%)。根据染色体核型的不同将患者分为低危组、中危组和高危组,不同基因在不同染色体核型中的变异率不相同,19例低危组患者基因变异频率由高到低为NRAS(n=4,21.05%)、KRAS(n=4,21.05%)、KIT(n=2,10.53%);96例中危组基因变异频率由高到低为NPM1(n=24,25.00%)、FLT3-ITD(n=20,20.83%)、DNMT3A(n=18,18.75%)、CEBPA(n=12,12.50%)、TET2(n=12,12.50%);19例高危组基因变异频率由高到低依次为ASXL1(n=7,21.05%)、NRAS(n=3,15.97%)、TP53(n=3,15.79%)、EZH2(n=2,10.53%),经统计学分析发现,KIT在低危组、NPM1、FLT3-ITD、DNMT3A在中危组、ASXL1在高危组的变异相对热点占比较高。结论AML患者基因变异频率较高,至少携带1个基因变异的患者大于76.1%,不同基因在不同的染色体核型患者中变异频率不一致,存在明显的优势变异,并且KIT、NPM1、FLT3-ITD、DNMT3A、ASXL1可以作为评估预后的因素之一。

Objective To analyze the characteristics of genetic variants in 134 patients diagnosed with Acute myeloid leukemia(AML).Methods Clinical data of the 134 patients with AML(non-acute promyelocytic leukemia)initially diagnosed at the 940th Hospital of the Joint Logistics Support Force of the Chinese People′s Liberation Army from June 2017 to June 2022 were retrospectively analyzed.Potential variants of AML-related genes were detected by next-generation sequencing,and the frequency of variants was analyzed by using SPSS v26.0 software,and likelihood ratioχ^(2) test and Fisher exact test were used for data analysis.Results The patients had included 72 males and 62 females,with a gender ratio of 1.7:1 and a median age of 51 years(9~86 years old).One hundred twenty patients(76.1%)had harbored at least one genetic variant,including 26(19.4%)having a single variant,27(20.1%)having two variants,and 49(36.6%)having≥3 variants.32(23.9%)had no detectable variants.Genetic variants detected in over 10%of the 134 patients had included NPM1(n=24,17.91%),FLT3-ITD(n=21,15.67%),DNMT3A(n=20,14.93%),CEBPA(single variant;n=14,10.45%),TET2(n=14,10.45%),and NRAS(n=14,10.45%).The patients were also divided into low risk,intermediate risk and high risk groups based on their chromosomal karyotypes.The mutational rates for genes in different groups have varied,with 19 patients from the low risk group harboring variants of NRAS(n=4,21.05%),KRAS(n=4,21.05%),and KIT(n=2,10.53%);and 96 patients from the intermediate risk group harboring variants of NPM1(n=24,25.00%),FLT3-ITD(n=20,20.83%),DNMT3A(n=18,18.75%),CEBPA(n=12,12.50%),and TET2 genes(n=12,12.50%).The mutational frequencies for the 19 patients from the high risk group were ASXL1(n=7,21.05%),NRAS(n=3,15.97%),TP53(n=3,15.79%),and EZH2(n=2,10.53%).A significant difference was found in the frequencies of KIT,NPM1,FLT3-ITD,DNMT3A,and ASXL1 gene variants among the low-risk,medium-risk,and high-risk groups.Conclusion AML patients have a high frequency for genetic variants,with 76.1%harboring at least one variant.The frequency of genetic variants have varied among patients with different chromosomal karyotypes,and there are apparent dominant variants.KIT,NPM1,FLT3-ITD,DNMT3A,and ASXL1 may be used as prognostic factors for evaluating their prognosis.