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

Blood 147, 1958-1969 (2026)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Myeloid Leukemia ; Locus (genetics) ; Leukemia ; Genome-wide Association Study ; Disease ; Myeloid ; Haematopoiesis ; Malignancy ; Myelodysplastic Syndromes; Coagulation-factor Deficiency; Clonal Hematopoiesis; Survival; Mutations; Aml; Susceptibility; Consolidation; Expression; Complex; Dnmt3a
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 147, Issue: 17, Pages: 1958-1969 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants Medical Research Council DiMeN Doctoral Training Programme
Blood Cancer UK