Genomic Profiles and Associated Survival Prognosticators in Black Patients with Acute Myeloid Leukemia

Background Our knowledge of the genomics of acute myeloid leukemia (AML), which serves as the basis of clinically used prognostic biomarkers and therapeutic advances (including targeted therapies), is almost exclusively based on data from patients (pts) of European ancestry. Methods We analyzed the exomes and transcriptomes of 100 Black AML pts at diagnosis who received intensive induction chemotherapy on Alliance for Clinical Trials in Oncology (Alliance) protocols. African Ancestry was confirmed by SNP analysis. We established their genetic landscape including somatic gene mutations, structural variants, gene fusions and associated gene expression. Somatic mutation frequency was compared to whole-exome sequencing of 741 White pts at diagnosis from the Beat AML cohort analyzed by identical workflow. Survival of Black pts was compared to 1,519 White pts treated on the same Alliance protocols. Multivariable analysis was used to identify clinical and molecular features associated with outcomes. Results We identified 162 recurrently mutated genes in Black AML pts. We detected different mutation frequencies for AML-associated genes based on ancestry, and mutations in genes not previously implicated in AML, including PHIP alterations in 7% of this cohort. 38 genes were mutated in 3-5% of Black pts but in