Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia

Lee SHR, Antillon-Klussmann F, Pei D, Yang W, Roberts KG, Li Z, Devidas M, Yang W, Najera C, Lin HP, Tan AM, Ariffin H, Cheng C, Evans WE, Hunger SP, Jeha S, Mullighan CG, Loh ML, Yeoh AEJ, Pui CH, Yang JJ. Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia. JAMA Oncol. 2022 Mar 1;8(3):354-363. doi: 10.1001/jamaoncol.2021.6826. PubMed PMID: 35084434; PubMed Central PMCID: PMC8796058.

This genetic association study comprehensively analyzed the molecular subtypes of ALL in 2428 patients from racially and ethnically diverse populations and described differences in leukemia somatic genomics across ancestries. Genetic ancestry was also associated with treatment outcomes, with Native American and African ancestries associated with poorer prognosis even with contemporary ALL therapy and after adjusting for ALL subtypes. This study suggests that the associations of genetic ancestry with ALL subtype and prognosis may underscore the biological basis of the racial and ethnic disparities in ALL, pointing to the need for molecular subtype–driven treatment individualization to help address racial and ethnic gaps in ALL survival.