Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger than white patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable analyses of Black patients, NPM1 and NRAS mutations were associated with inferior disease-free and IDH1 and IDH2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction.

来自血统多样化人群的急性髓性白血病 （AML） 患者的基因组谱和预后生物标志物尚未得到充分探索。我们分析了 100 例经基因组证实的非洲血统的 AML 患者的外显子组和转录组 （Black;Alliance） 并将他们的体细胞突变频率与 323 名自我报告的白人 AML 患者的体细胞突变频率进行了比较，其中 55% 的患者具有基因组学证实的欧洲血统（白人;BeatAML 的 BeatAML）。在这里，我们发现黑人患者复发的 162 种基因突变中有 73%，包括在 7% 的患者中检测到的迄今为止未报道的 PHIP 改变，是在一名白人患者中发现或未检测到的。患有骨髓增生异常相关 AML 的黑人患者比白人患者年轻，这表明存在内在和/或外源性异型增生引起的压力源。在对黑人患者的多变量分析中，NPM1 和 NRAS 突变与较差的无病和 IDH1 和 IDH2 突变相关，总生存期降低。具有 NPM1 突变的黑人和白人的炎症特征、细胞类型分布和转录特征不同。将血统特异性风险标志物纳入 2022 年欧洲 LeukemiaNet 遗传风险分层改变了三分之一黑人患者的风险组分配，并改善了他们的结果预测。