急性髓系白血病 (AML) 可表现为新发 AML (dn-AML) 或继发性 AML (s-AML)，其中 s-AML 与较差的生存率和独特的基因组特征相关。造成这种差异的根本原因仍有待阐明。在这项多中心研究中，采用下一代测序（NGS）技术对2020年6月至2023年5月721名患者的AML突变情况进行了调查。93.34%的个体中观察到基因突变，且变异复杂（超过3个基因）。其中 63.10% 存在突变）。 TET2、ASXL1、DNMT3A、TP53 和 SRSF2 突变在老年患者中的患病率较高，而 WT1 和 KIT 突变在年轻患者中更常见。 BCOR、BCORL1、ZRSR2、ASXL1 和 SRSF2 在男性中表现出较高的突变频率。此外，ASXL1、NRAS、PPMID、SRSF2、TP53 和 U2AF1 突变在 s-AML 患者中更为常见，其中 PPM1D 更常与治疗相关 AML (t-AML) 相关。高龄和白细胞增多分别是两种类型 AML 的不良预后因素；然而，与 dn-AML 病例相比，s-AML 患者表现出更多的单基因不良预后因素（s-AML 中的 ASXL1、PPM1D、TP53 和 U2AF1 与 dn-AML 中的 FLT3、TP53 和 U2AF1）。年龄和性别相关的基因突变表明表观遗传变化可能是 AML 发病机制的关键。与 dn-AML 相比，s-AML 的预后较差，可能是由于 s-AML 患者年龄较大且预后不良的基因突变较多。这些发现可以通过确定潜在的治疗靶点和风险分层生物标志物来改善 AML 的诊断和治疗。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.