@article{10902/38623,
year = {2025},
url = {https://hdl.handle.net/10902/38623},
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.},
organization = {This work was primarily funded by the US National Cancer Institute (R01
CA239701, ME Scheurer/LG Spector, principal investigators). Sample
collection in Texas was supported in part by the Adolescent and
Childhood Cancer Epidemiology and Susceptibility Service, funded by
the Cancer Prevention and Research Institute of Texas (RP160771 and
RP210064, ME Scheurer, principal investigator). C. Im is also supported
by the US National Cancer Institute (R01 CA283333, C Im/Z Wang,
principal investigators), the Children’s Cancer Research Fund, and University of Minnesota Foundation Pediatric Scholar Award. The CCRLP
GWAS study was supported by R01CA155461 (J Wiemels/X Ma), which
funded the acquisition of the genetic data. The biospecimens and data
used in the CCRLP study were obtained from the California Biobank
Program (SIS request #1380) and related collection of cancer incidence
data was supported by the California Department of Public Health as
part of the statewide cancer-reporting program mandated by California
Health and Safety Code Section 103885; the National Cancer Institute’s
Surveillance, Epidemiology and End Results Program under contract
HHSN261201000140C awarded to the Cancer Prevention Institute of
California, contract HHSN261201000035C awarded to the University of
Southern California, and contract HHSN261201000034C awarded to
the Public Health Institute; and the Centers for Disease Control and
Prevention’s National Program of Cancer Registries, under agreement
U58DP003862-01 awarded to the California Department of Public
Health. Children’s Oncology. Group contributions were supported by
U10CA180886 (NCTN Operations Center Grant), U10CA180899 (NCTN
Statistics & Data Center Grant), and U24CA196173 (COG Biospecimen
Bank Grant). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Institutes of Health.},
publisher = {Nature Publishing Group},
publisher = {Nature Communications, 16(1), 8974},
title = {Genome-wide association study of childhood B-cell acute lymphoblastic leukemia reveals novel African ancestry-specific susceptibility loci},
author = {Im, Cindy and Raduski, Andrew R. and Mills, Lauren J. and Bhattarai, Kashi Raj and Mobley, Robert J. and Barnett, Kelly R. and Lu, Zhanni and Liao, Kenneth and Anderson, Nathan and Johnson, Rebecca A. and Langer, Erica and Hooten, Anthony J. and Seif, Alix E. and Bernt, Kathrin M. and Tsang, Matthew and Mamou, Brandon A. and Gil de Gómez Sesma, Luis and Wolfson, Julie A and Friedman, Danielle N. and Shukla, Neerav},
}