Language
English
Publication Date
10-22-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-64337-7
PMID
41125582
PMCID
PMC12546916
PubMedCentral® Posted Date
10-22-2025
PubMedCentral® Full Text Version
Post-print
Abstract
B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance (P < 5 × 10−8) after meta-analysis. Two loci were established trans-ancestral susceptibility regions (IKZF1, ARID5B), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P = 4.8 × 10−3). Novel risk variants were also associated with subtype-specific disease (P < 0.05), including higher susceptibility for a subtype overrepresented in African American children (TCF3-PBX1) and lower susceptibility for a subtype with excellent prognosis (ETV6-RUNX1). Functional experiments revealed novel B-ALL risk variants had allele-specific differences in transcriptional activity (P < 0.05) in B-cell and leukemia cell lines. These findings shed insights into ancestry-related differences in leukemogenesis and prognosis.
Keywords
Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Child, Black or African American, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Female, Child, Preschool, Transcription Factors, Polymorphism, Single Nucleotide, Ikaros Transcription Factor, DNA-Binding Proteins, Adolescent, Alleles, Oncogene Proteins, Fusion, Core Binding Factor Alpha 2 Subunit, Infant, Case-Control Studies, Prognosis, White, ETS Translocation Variant 6 Protein, Genome-wide association studies, Cancer genetics, Paediatric cancer, Acute lymphocytic leukaemia, Cancer epidemiology
Published Open-Access
yes
Recommended Citation
Im, Cindy; Raduski, Andrew R; Mills, Lauren J; et al., "Genome-Wide Association Study of Childhood B-cell Acute Lymphoblastic Leukemia Reveals Novel African Ancestry-Specific Susceptibility Loci" (2025). Faculty, Staff and Students Publications. 6377.
https://digitalcommons.library.tmc.edu/baylor_docs/6377