Genome-wide association study of childhood B-cell acute lymphoblastic leukemia reveals novel African ancestry-specific susceptibility loci.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 41125582.
- Also identified by DOI 10.1038/s41467-025-64337-7 and PMC identifier 12546916.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-8</sup>) 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<sup>-3</sup>). 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.
Medical subject headings
- Genetic Predisposition to Disease
- Black or African American
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma