Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences the risk of acute myeloid leukemia
Ranasinghe, Diyanath Lin, Wei-Yu Fordham, Sarah E Alharbi, Abrar Sunter, Nicola J Elstob, Claire Nahari, Mohammed H Xu, Yaobo Park, Catherine Hungate, Eric
Ranasinghe, Diyanath
Lin, Wei-Yu
Fordham, Sarah E
Alharbi, Abrar
Sunter, Nicola J
Elstob, Claire
Nahari, Mohammed H
Xu, Yaobo
Park, Catherine
Hungate, Eric
Abstract
Acute myeloid leukemia (AML) is a complex hematologic malignancy with multiple disease subgroups 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 4 published GWAS plus 2 new GWAS, totaling 4710 AML cases and 12 938 controls. We identify a new genome-wide significant risk locus for pan-AML at 2p23.3 (rs4665765; P = 1.35 × 10-8; EFR3B, POMC, DNMT3A, and DNAJC27), which also significantly associates with patient survival (P = 6.09 × 10-3). Our analysis also identifies 3 new genome-wide significant risk loci for disease subgroups, including AML with deletions of chromosome 5 and/or 7 at 1q23.3 (rs12078864; P = 7.0 × 10-10; DUSP23) and cytogenetically complex AML at 2q33.3 (rs12988876; P = 3.28 × 10-8; PARD3B) and 2p21 (rs79918355; P = 1.60 × 10-9; EPCAM). We also investigated loci previously associated with the risk of clonal hematopoiesis (CH) or CH of indeterminate potential and identified several variants associated with the risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease subgroup specific risk loci.
MIDER Authors
Affiliations
Date
2026-04-23
Type
Article
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Citation
Ranasinghe D, Lin WY, Fordham SE, Alharbi A, Sunter NJ, Elstob C, Nahari MH, Xu Y, Park C, Hungate E, Quante A, Strauch K, Gieger C, Skol A, Rahman T, Sucheston-Campbell L, Hahn T, Clay-Gilmour AI, Jones GL, Marr HJ, Jackson GH, Menne T, Collin M, Ivey A, Hills RK, Burnett AK, Russell NH, Fitzgibbon J, Larson RA, Le Beau MM, Stock W, Heidenreich O, Enshaei A, Gunasinghe D, Hawking ZL, Heslop H, Nandana D, Di B, Plokhuta A, Brown IT, Allsup DJ, Houlston RS, Collins A, Milne P, Norden J, Dickinson AM, Lendrem C, Daly AK, Palm L, Piechocki K, Jeffries S, Bornhäuser M, Röllig C, Altmann H, Ruhnke L, Kunadt D, Wagenführ L, Cordell HJ, Darlay R, Andersen MK, Fontana MC, Martinelli G, Marconi G, Sanz MA, Cervera J, Gómez-Seguí I, Cluzeau T, Moreilhon C, Raynaud S, Sill H, Voso MT, Dombret H, Cheok M, Preudhomme C, Gale RE, Linch D, Weisinger J, Masszi A, Nowak D, Hofmann WK, Gilkes A, Porkka K, Milosevic Feenstra JD, Kralovics R, Wang J, Meggendorfer M, Haferlach T, Krizsán S, Bödör C, Parkin B, Malek SN, Stölzel F, Onel K, Allan JM. Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences the risk of acute myeloid leukemia. Blood. 2026 Apr 23;147(17):1958-1969. doi: 10.1182/blood.2025031266