本研究的目的是验证新的2022年欧洲白血病网络（European Leukemia Net，ELN）的遗传风险分层标准，以老年急性髓系白血病（acute myeloid leukemia，AML）患者为对象，并确定与存活结果相关的具有类似细胞遗传和突变特性的集群。我们将研究三种治疗组中最可能形成的集群：强化化疗（intensive chemotherapy，IC）、低甲基化剂（hypomethylating agents，HMAs）单用以及HMAs联用维奈替克（venetoclax）（HMA/VEN）。该研究纳入了2017年7月至2021年10月期间接受IC治疗的131名患者、HMA治疗的76名患者以及HMA/VEN治疗的72名患者，共279例60岁以上患者。根据ELN 2022年风险分层标准，各组之间的生存差异无显著性。无监督层次聚类分析鉴定出九个基因组集群（C1-9），其存活结果因治疗类型的不同而不同。例如，C4（主要与核心结合因子AML相关）在IC组中显示出良好的预后，但在HMA组或HMA/VEN组中却没有。在许多集群（C1、2、3和5）中，HMA/VEN组的结果比HMA组好；然而，相较于HMA单用，在C7和C9（主要与-5、del(5q)、-7、-17/abn(17p)、复杂核型和突变TP53有关）中，添加VEN到HMA或IC并未改善生存结果。本研究强调了ELN遗传风险分层在老年AML患者中的局限性，并强调有必要采用更全面的方法，考虑共存的体细胞突变，以指导老年AML患者的治疗选择。

This study aimed to validate the new European Leukemia Net (ELN) 2022 criteria for genetic risk stratification in older adults with acute myeloid leukemia (AML) and to determine the most likely set of clusters of similar cytogenetic and mutation properties correlated with survival outcomes in three treatment groups: intensive chemotherapy (IC), hypomethylating agents (HMAs) alone, and HMAs plus venetoclax (HMA/VEN). The study included 279 patients (≥60 years) who received IC (n=131), HMA (n=76), and HMA/VEN (n=72) between July 2017 and October 2021. No significant differences were observed in survival among the groups according to ELN 2022 risk stratification. Unsupervised hierarchical clustering analysis identified nine genomic clusters (C1-9) with varying survival outcomes depending on treatment type. For example, C4 (predominant for core binding factor-AML) displayed a favorable prognosis in the IC group, but not in the HMA or HMA/VEN group. The HMA/VEN group had better outcomes than the HMA group in many clusters (C1, 2, 3, and 5); however, the addition of VEN to HMA or IC did not improve the survival outcomes compared with those of HMA alone in C7 and C9 [predominant for -5, del(5q), -7, -17/abn(17p), complex karyotypes, and mutated TP53 ]. The study highlights the limitations of ELN genetic risk stratification in older adults with AML. It emphasizes the need for a more comprehensive approach that considers co-occurring somatic mutations to guide treatment selection in older adults with AML potentially.