Journal Article

DKFZ-2026-01007

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences the risk of acute myeloid leukemia.

Ranasinghe, D. ; Lin, W.-Y. ; Fordham, S. E. ; Alharbi, A. ; Sunter, N. J. ; Elstob, C. ; Nahari, M. H. ; Xu, Y. ; Park, C. ; Hungate, E. ; Quante, A. ; Strauch, K. ; Gieger, C. ; Skol, A. ; Rahman, T. ; Sucheston-Campbell, L. ; Hahn, T. ; Clay-Gilmour, A. I. ; Jones, G. L. ; Marr, H. J. ; Jackson, G. H. ; Menne, T. ; Collin, M. ; Ivey, A. ; Hills, R. K. ; Burnett, A. K. ; Russell, N. H. ; Fitzgibbon, J. ; Larson, R. A. ; Le Beau, M. M. ; Stock, W. ; Heidenreich, O. ; Enshaei, A. ; Gunasinghe, D. ; Hawking, Z. L. ; Heslop, H. ; Nandana, D. ; Di, B. ; Plokhuta, A. ; Brown, I. T. ; Allsup, D. J. ; Houlston, R. S. ; Collins, A. ; Milne, P. ; Norden, J. ; Dickinson, A. M. ; Lendrem, C. ; Daly, A. K. ; Palm, L. ; Piechocki, K. ; Jeffries, S. ; Bornhäuser, M.DKFZ* ; Röllig, C. ; Altmann, H. ; Ruhnke, L. ; Kunadt, D. ; Wagenführ, L. ; Cordell, H. J. ; Darlay, R. ; Andersen, M. K. ; Fontana, M. C. ; Martinelli, G. ; Marconi, G. ; Sanz, M. A. ; Cervera, J. ; Gómez-Seguí, I. ; Cluzeau, T. ; Moreilhon, C. ; Raynaud, S. ; Sill, H. ; Voso, M. T. ; Dombret, H. ; Cheok, M. ; Preudhomme, C. ; Gale, R. E. ; Linch, D. ; Weisinger, J. ; Masszi, A. ; Nowak, D. ; Hofmann, W.-K. ; Gilkes, A. ; Porkka, K. ; Milosevic Feenstra, J. D. ; Kralovics, R. ; Wang, J. ; Meggendorfer, M. ; Haferlach, T. ; Krizsán, S. ; Bödör, C. ; Parkin, B. ; Malek, S. N. ; Stölzel, F. ; Onel, K. ; Allan, J. M.

2026
American Society of Hematology Washington, DC

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.

Keyword(s): Humans (MeSH) ; Leukemia, Myeloid, Acute: genetics (MeSH) ; Genome-Wide Association Study (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Chromosomes, Human, Pair 2: genetics (MeSH) ; Chromosomes, Human, Pair 1: genetics (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Male (MeSH) ; Case-Control Studies (MeSH)

Note: #NCTZFB9#

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Contributing Institute(s):

1. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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