Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences risk of acute myeloid leukemia

Ranasinghe, Diyanath, Lin, Wei-Yu, Fordham, Sarah E., Alharbi, Abrar A., Sunter, Nicola J., Elstob, Claire, Nahari, Mohammed H., Xu, Yaobo, Park, Catherine, Hungate, Eric, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew D., Rahman, Thahira, Thahira-Campbell, Lara, Hahn, Theresa, Clay-Gilmour, Alyssa Ione, Jones, Gail L., Marr, Helen J. and Gilkes, Amanda 2026. Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences risk of acute myeloid leukemia. Blood 147 (17) , pp. 1958-1969. 10.1182/blood.2025031266

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Abstract

Acute myeloid leukemia (AML) is a complex hematological malignancy with multiple disease sub-groups defined by somatic mutations and heterogeneous outcomes. Although genome-wide association studies (GWAS) have identified a small number of common genetic variants influencing AML risk, the heritable component of this disease outside of familial susceptibility remains largely undefined. Here we perform a meta-analysis of four published GWAS plus two new GWAS, totalling 4710 AML cases and 12938 controls. We identify a new genome-wide significant risk locus for pan-AML at 2p23.3 (rs4665765; P=1.35x10-8; EFR3B, POMC, DNMT3A, DNAJC27) which also significantly associates with patient survival (P=6.09x10-3). Our analysis also identifies three new genome-wide significant risk loci for disease sub-groups, including AML with deletions of chromosome 5 and/or 7 at 1q23.3 (rs12078864; P=7.0x10-10; DUSP23) and cytogenetically complex AML at 2q33.3 (rs12988876; P=3.28x10-8; PARD3B) and 2p21 (rs79918355; P=1.60x10-9; EPCAM). We also investigated loci previously associated with risk of clonal hematopoiesis (CH) or clonal hematopoiesis of indeterminate potential (CHIP) and identified several variants associated with risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease sub-group specific risk loci.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	RRS applied For the full list of authors, please refer to the article webpage https://doi.org/10.1182/blood.2025031266
Publisher:	American Society of Hematology (ASH Publications)
ISSN:	0006-4971
Date of First Compliant Deposit:	12 February 2026
Date of Acceptance:	19 December 2025
Last Modified:	06 May 2026 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/184718

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