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

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.

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Journal
Blood
Published
2026-01-29
DOI
https://doi.org/10.1182/blood.2025031266
Citations
1
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
35.41

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article

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

Li Ni, Júlia Weisinger, Heidi Altmann, Louise Palm et al.
1 citations
Blood
Acute Myeloid Leukemia Research
35.41
article

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

Li Ni, Júlia Weisinger, Heidi Altmann, Louise Palm, Imogen Brown, Clare Lendrem, Ann K. Daly, Zoe Hawking, Chimène Moreilhon, Csaba Bödör, Kim Piechocki, Adam Ivey, giovanni marconi, Abrar Alharbi, G. L. Jones, Maria Chiara Fontana, Amanda Gilkes, Matthew Collin, H. Cordell, C. Preudhomme, Nigel H. Russell, Manja Meggendorfer, Kenan Onel, Anne S. Quante, Jelena D. Milosevic Feenstra, Sarah Fordham, Robert K. Hills, Friedrich Stölzel, C Park, Desireé Kunadt, Olaf T Heidenreich, Paul Milne, Daniel Nowak, Lisa Wagenführ, Rosemary E. Gale, Graham Jackson, R. Kralovics, T. Cluzeau, Leo Ruhnke, J. Arguedas Cervera, Claire Elstob, Andrew Collins, Sally Jeffries, G Martinelli, Tobias Menne, Meyling Cheok, Devi Nandana, Szilvia Krizsán, Jude Fitzgibbon, Junke Wang, Manuel Sanz, Gómez-Seguí Inés, Lara Sucheston‐Campbell, Sophie Raynaud, DC Linch, Sami N. Malek, Thahira Rahman, Dumni Gunasinghe, AM Dickinson, Diyanath Ranasinghe, Theresa Hahn, Heinz Sill, Jean Norden, Martin Bornhäuser, Amir Enshaei, Michelle M. Le Beau, David J Allsup, Rebecca Darlay, Yaobo Xu, Wolf Karsten Hofmann, Anna Plokhuta, Andrew D. Skol, Christoph Röllig, Richard S. Houlston, Eric Hungate, Mohammed H Nahari, Nicola J Sunter, Hervé Dombret, Christian Gieger, Helen J Marr, Andras Masszi, Brian L Parkin, Alan K Burnett, Torsten Haferlach, Holly S Heslop, Wei-Yu Lin, Wendy Stock, Mette K. Andersen, Konstantin Strauch, Bingjing Di, Alyssa Ione Clay-Gilmour
article en
1 citations

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.

Blood
Semmelweis University (HU), University of Rome Tor Vergata (IT), Roswell Park Comprehensive Cancer Center (US), Centre National de la Recherche Scientifique (FR), The University of Texas MD Anderson Cancer Center (US), Institute of Cancer Research (GB), Inserm (FR), University of South Carolina (US), Queen Mary University of London (GB), King's College London (GB), Wayne State University (US), Johannes Gutenberg University Mainz (DE), Guy's and St Thomas' NHS Foundation Trust (GB), Medical University of Graz (AT), Université Paris Cité (FR), Heidelberg University (DE), Université de Lille (FR), Taibah University (SA), University of Michigan (US), Helsinki University Hospital (FI), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Freeman Hospital (GB), The Alfred Hospital (AU), University Hospital Heidelberg (DE), TUM Klinikum (DE), Rigshospitalet (DK), Helmholtz Zentrum München (DE), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Hospital Universitari i Politècnic La Fe (ES), University of Oxford (GB), University of Chicago (US), Blood Cancer UK (GB), Munich Leukemia Laboratory (Germany) (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Birmingham Women's Hospital (GB), Michigan United (US), University Hospital Schleswig-Holstein (DE), National Institute of Oncology (HU), Princess Máxima Center (NL), Hôpital Pasteur (FR), University Medical Centre Mannheim (DE), University Hospital Carl Gustav Carus (DE), Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE), Clinical Research Center Kiel (DE), University of Southampton (GB), University College London (GB), Najran University (SA), Elmhurst University (US), Hull York Medical School (GB), Medical University of Vienna (AT), Technische Universität Dresden (DE), University of Newcastle Australia (AU), University of Glasgow (GB), Cardiff University (GB), Newcastle University (GB), University of Lübeck (DE), University of Bologna (IT)
Terveyden ja hyvinvoinnin laitos, Blood Cancer UK, Medical Research Council
Good health and well-being
Openalex Percentile: Top 1%
Acute Myeloid Leukemia Research
35.41
DOIOpen Access PDFOpenAlex
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