Accès ouvert déclaré2026article
Common variation at 1q23.3, 2p23.3, 2q33.3, and 2p21 influences the risk of acute myeloid leukemia
Diyanath Ranasinghe, Wei-Yu Lin, Sarah Fordham, Abrar Alharbi, Nicola J Sunter, Claire Elstob, Mohammed H Nahari, Yaobo Xu, C Park, Eric Hungate, Anne S. Quante, Konstantin Strauch, Christian Gieger, Andrew D. Skol, Thahira Rahman, Lara Sucheston‐Campbell, Theresa Hahn, Alyssa Ione Clay-Gilmour, G. L. Jones, Helen J Marr, Graham Jackson, Tobias Menne, Matthew Collin, Adam Ivey, Robert K. Hills, Alan K Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Amir Enshaei, Dumni Gunasinghe, Zoe Hawking, Holly S Heslop, Devi Nandana, Bingjing Di, Anna Plokhuta, Imogen Brown, David Allsup, Richard S. Houlston, Andrew Collins, Paul Milne, Jean Norden, AM Dickinson, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhäuser, Christoph Röllig, Heidi Altmann, Leo Ruhnke, Desireé Kunadt, Lisa Wagenführ, H. Cordell, Rebecca Darlay, Mette K. Andersen, Maria Chiara Fontana, G Martinelli, Giovanni Marconi, Miguel A. Sanz, J. Arguedas Cervera, Gómez-Seguí Inés, T. Cluzeau, Chimène Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Hervé Dombret, Meyling Cheok, C. Preudhomme, Rosemary E. Gale, DC Linch, Júlia Weisinger, András Masszi, Daniel Nowak, Wolf Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Róbert Královics, Junke Wang, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Brian Parkin, Sami N. Malek, Friedrich Stölzel, Kenan Onel, James M. Allan
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Résumé fourni par la source
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.
Sujets associés
Acute Myeloid Leukemia ResearchGenomics and Rare DiseasesAcute Lymphoblastic Leukemia research