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2016-11-11

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cc-by (c) Kandaswamy, Radhika et al., 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/119703

Genetic predisposition to chronic lymphocytic leukemia is mediated by a BMF super-enhancer polymorphism

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Recurs relacionat

https://doi.org/10.1016/j.celrep.2016.07.053

Resum

Chronic lymphocytic leukemia (CLL) is an adult B cell malignancy. Genome-wide association studies show that variation at 15q15.1 influences CLL risk. We deciphered the causal variant at 15q15.1 and the mechanism by which it influences tumorigenesis. We imputed all possible genotypes across the locus and then mapped highly associated SNPs to areas of chromatin accessibility, evolutionary conservation, and transcription factor binding. SNP rs539846 C>A, the most highly associated variant (p = 1.42 × 10(-13), odds ratio = 1.35), localizes to a super-enhancer defined by extensive histone H3 lysine 27 acetylation in intron 3 of B cell lymphoma 2 (BCL2)-modifying factor (BMF). The rs539846-A risk allele alters a conserved RELA-binding motif, disrupts RELA binding, and is associated with decreased BMF expression in CLL. These findings are consistent with rs539846 influencing CLL susceptibility through differential RELA binding, with direct modulation of BMF expression impacting on anti-apoptotic BCL2, a hallmark of oncogenic dependency in CLL.

Matèries

Leucèmia limfocítica crònica, Cèl·lules B, Genètica humana, Limfòcits, Factors de transcripció

Matèries (anglès)

Chronic lymphocytic leukemia, B cells, Human genetics, Lymphocytes, Transcription factors

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Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

KANDASWAMY, Radhika, SAVA, Georgina p., SPEEDY, Helen e., BEÀ BOBET, Sílvia m., MARTÍN-SUBERO, José ignacio, STUDD, James b., MIGLIORINI, Gabriele, LAW, Philip j., PUENTE, Xose s., MARTÍN GARCÍA, David, SALAVERRIA FRIGOLA, Itziar, GUTIÉRREZ-ABRIL, Jesús, LÓPEZ-OTIN, Carlos, CATOVSKY, Daniel, ALLAN, James m., CAMPO GÜERRI, Elias, HOULSTON, Richard s.. Genetic predisposition to chronic lymphocytic leukemia is mediated by a BMF super-enhancer polymorphism. _Stem Cell Reports_. 2016. Vol. 16, núm. 8, pàgs. 2061-2067. [consulta: 15 de gener de 2026]. ISSN: 2213-6711. [Disponible a: https://hdl.handle.net/2445/119703]

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