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目的:探讨初诊急性髓系白血病（AML）患者的基因突变分布特点及其与预后的关系。方法:回顾性分析2016年5月至2019年12月就诊于空军军医大学第二附属医院（唐都医院）的225例初诊AML（非急性早幼粒细胞白血病）患者的临床资料。采用二代测序技术检测与AML、骨髓增生异常综合征（MDS）、骨髓增殖性肿瘤（MPN）相关的34个基因突变，分析总体基因突变的分布及其在不同年龄组间分布的差异，对比不同基因突变患者生存的差异，采用Cox回归模型分析<60岁和≥60岁患者生存影响因素。结果:225例患者共检测到496个基因突变位点，中位变异等位基因频率（VAF）为38.55%（1.00%~94.86%），患者中位突变基因数为3个/例（0~8个/例）。突变发生频率较高的基因有ASXL1、CEBPA、NPM1、NRAS、FLT3-ITD、DNMT3A、IDH2、TET2、RUNX1、IDH1。≥60岁患者（56例）TET2、SRSF2、SF3B1基因突变发生率均高于<60岁患者（169例），差异均有统计学意义（均n P<0.01）；在≥60岁患者中同时发生3种及以上基因突变者比例较<60岁患者高[53.6%（30/56）比33.1%（56/169），n χ2＝7.44，n P＝0.006]。TP53、RUNX1或FLT3-ITD基因突变患者的总生存（OS）较各基因野生型患者差，CEBPA基因双突变患者OS优于其单突变或野生型患者，差异均有统计学意义（均n P<0.05）。多因素Cox回归分析结果显示，CEBPA（n HR＝0.279，95% n CI 0.084~0.926，n P＝0.037）、TET2（n HR＝2.611，95% n CI 1.115~6.111，n P＝0.027）和TP53（n HR＝3.609，95% n CI 1.159~11.234，n P＝0.027）基因突变是<60岁AML患者生存的独立影响因素，ASXL1（n HR＝3.523，95% n CI 1.385~8.962，n P＝0.008）、FLT3-ITD（n HR＝4.618，95% n CI 1.813~11.762，n P＝0.001）和NRAS（n HR＝2.896，95% n CI 1.166~7.000，n P＝0.022）基因突变是≥60岁AML患者生存的独立危险因素。n 结论:不同年龄AML患者基因突变分布存在差异，老年患者更易同时合并多种基因突变。除了已知的CEBPA双突变和TP53、ASXL1、RUNX1等基因突变外，TET2和NRAS基因突变可能也是影响预后的因素。“,”Objective:To investigate the distribution characteristics of gene mutations and their relationship with prognosis in newly diagnosed patients with acute myeloid leukemia (AML).Methods:The clinical data of 225 newly diagnosed AML (non-acute promyelocytic leukemia) patients in the Second Affiliated Hospital (Tangdu Hospital) of Air Force Medical University from May 2016 to December 2019 were retrospectively analyzed. Thirty-four gene mutations related to AML, myelodyplastic syndrome (MDS) and myeloproliterative neoplasms (MPN) were detected by second-generation sequencing. The distribution of all gene mutations and its difference among different age groups were analyzed, and the differences in survival of patients with different gene mutations were compared. The Cox regression model was employed to analyze the survival influencing factors of patients aged <60 years old and ≥60 years old.Results:A total of 496 gene mutation sites were detected in 225 patients, with a median variant allel frequency (VAF) of 38.55% (1.00%-94.86%) and a median gene mutations of 3/case (0-8/case). The genes with high mutation frequency were ASXL1, CEBPA, NPM1, NRAS, FLT3-ITD, DNMT3A, IDH2, TET2, RUNX1, and IDH1. The gene mutation rates of TET2, SRSF2 and SF3B1 in patients aged ≥60 years old (56 cases) were higher than those in patients aged <60 years old (169 cases), and the differences were statistically significant (all n P < 0.01). The proportion of patients aged ≥60 years old with 3 or more gene mutations was higher than that of patients aged <60 years old [53.6% (30/56) vs. 33.1% (56/169), n χ2 = 7.44, n P = 0.006]. The overall survival (OS) of patients with TP53, RUNX1 or FLT3-ITD gene mutation was worse than that of wild-type patients, the OS of patients with CEBPA double mutations was better than that of patients with CEBPA single mutation or wild-type, and the differences were statistically significant (all n P < 0.05). Multivariate Cox regression analysis showed that CEBPA ( n HR = 0.279, 95% n CI 0.084-0.926, n P = 0.037), TET2 (n HR = 2.611, 95% n CI 1.115-6.111, n P = 0.027) and TP53 (n HR = 3.609, 95% n CI 1.159-11.234, n P = 0.027) gene mutations were independent factors affecting the survival of AML patients aged <60 years old, ASXL1 ( n HR = 3.523, 95% n CI 1.385-8.962, n P = 0.008), FLT3-ITD (n HR = 4.618, 95% n CI 1.813-11.762, n P = 0.001) and NRAS (n HR = 2.896, 95% n CI 1.166-7.000, n P = 0.022) were independent risk factors of the survival of AML patients aged ≥60 years old.n Conclusions:There are differences in the distribution of gene mutations among AML patients with different age, and the elderly patients are more likely to have multiple gene mutations at the same time. In addition to the currently known CEBPA double mutations, TP53, ASXL1, RUNX1 and other gene mutations, TET2 and NRAS gene mutations may also be factors affecting the prognosis.