多组学分析可确定非裔美国急性髓系白血病患者的生存预测因子。
Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia.
发表日期：2024 Oct 04
作者：
Andrew Stiff, Maarten Fornerod, Bailee N Kain, Deedra Nicolet, Benjamin J Kelly, Katherine E Miller, Krzysztof Mrózek, Isaiah Boateng, Audrey Bollas, Elizabeth A R Garfinkle, Omolegho Momoh, Foluke A Fasola, Hannah O Olawumi, Nuria Mencia-Trinchant, Jean F Kloppers, Anne-Cecilia van Marle, Eileen Hu, Saranga Wijeratne, Gregory Wheeler, Christopher J Walker, Jill Buss, Adrienne Heyrosa, Helee Desai, Andrea Laganson, Ethan Hamp, Yazan Abu-Shihab, Hasan Abaza, Parker Kronen, Sidharth Sen, Megan E Johnstone, Kate Quinn, Ben Wronowski, Erin Hertlein, Linde A Miles, Alice S Mims, Christopher C Oakes, James S Blachly, Karilyn T Larkin, Bethany Mundy-Bosse, Andrew J Carroll, Bayard L Powell, Jonathan E Kolitz, Richard M Stone, Cassandra Duarte, Diana Abbott, Maria L Amaya, Craig T Jordan, Geoffrey L Uy, Wendy Stock, Kellie J Archer, Electra D Paskett, Monica L Guzman, Ross L Levine, Kamal Menghrajani, Debyani Chakravarty, Michael F Berger, Daniel Bottomly, Shannon K McWeeney, Jeffrey W Tyner, John C Byrd, Nathan Salomonis, H Leighton Grimes, Elaine R Mardis, Ann-Kathrin Eisfeld
来源：
NATURE GENETICS
摘要：
来自不同血统人群的急性髓系白血病 (AML) 患者的基因组谱和预后生物标志物尚未得到充分研究。我们分析了 100 名经基因组证实具有非洲血统的 AML 患者（黑人；联盟）的外显子组和转录组，并将他们的体细胞突变频率与 323 名自我报告的 AML 白人患者进行了比较，其中 55% 具有经基因组证实的欧洲血统（白人） ; 击败AML）。在这里，我们发现，在黑人患者中复发的 162 个基因突变中，有 73% 在一名白人患者中发现或未检测到，其中包括 7% 的患者中检测到的迄今为止未报告的 PHIP 改变。患有骨髓增生异常相关 AML 的黑人患者比白人患者年轻，表明存在内在和/或外在的导致骨髓增生异常的压力源。在对黑人患者的多变量分析中，NPM1 和 NRAS 突变与较差的无病状态相关，而 IDH1 和 IDH2 突变则与总生存率降低相关。具有 NPM1 突变的黑人和白人患者的炎症特征、细胞类型分布和转录特征不同。将血统特异性风险标记纳入 2022 年欧洲白血病网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。© 2024。作者。
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.© 2024. The Author(s).