Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism

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...

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Published inCell reports (Cambridge) Vol. 16; no. 8; pp. 2061 - 2067
Main Authors Kandaswamy, Radhika, Sava, Georgina P., Speedy, Helen E., Beà, Sílvia, Martín-Subero, José I., Studd, James B., Migliorini, Gabriele, Law, Philip J., Puente, Xose S., Martín-García, David, Salaverria, Itziar, Gutiérrez-Abril, Jesús, López-Otín, Carlos, Catovsky, Daniel, Allan, James M., Campo, Elías, Houlston, Richard S.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 23.08.2016
Cell Press
Elsevier
Subjects
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Alleles
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
Binding Sites
Cell Line, Tumor
Chromatin - chemistry
Chromatin - metabolism
Chromosome Mapping
Chromosomes, Human, Pair 15
Enhancer Elements, Genetic
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Histones - genetics
Histones - metabolism
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Odds Ratio
Polymorphism, Single Nucleotide
Protein Binding
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Risk
Transcription Factor RelA - genetics
Transcription Factor RelA - metabolism
Online AccessGet full text
ISSN2211-1247
2211-1247
DOI10.1016/j.celrep.2016.07.053

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Abstract 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. [Display omitted] •SNP rs539846 underlies 15q15.1 association with chronic lymphocytic leukemia•rs539846 resides in a B cell super-enhancer, disrupting a conserved RELA-binding site•The rs539846 risk allele (A) reduces enhancer activity and RELA binding in CLL•rs539846-A confers lower BMF expression Kandaswamy et al. find that SNP rs539846 underlies the 15q15.1 chronic lymphocytic leukemia risk locus. Follow-up data demonstrate that rs539846 resides within a transcriptional enhancer and alters RELA binding at a conserved site. The rs539846-A risk allele results in reduced RELA-mediated enhancer activity and lower expression of BCL-2-modifying factor.
AbstractList 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.
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. • SNP rs539846 underlies 15q15.1 association with chronic lymphocytic leukemia • rs539846 resides in a B cell super-enhancer, disrupting a conserved RELA-binding site • The rs539846 risk allele (A) reduces enhancer activity and RELA binding in CLL • rs539846-A confers lower BMF expression Kandaswamy et al. find that SNP rs539846 underlies the 15q15.1 chronic lymphocytic leukemia risk locus. Follow-up data demonstrate that rs539846 resides within a transcriptional enhancer and alters RELA binding at a conserved site. The rs539846-A risk allele results in reduced RELA-mediated enhancer activity and lower expression of BCL-2-modifying factor.
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. [Display omitted] •SNP rs539846 underlies 15q15.1 association with chronic lymphocytic leukemia•rs539846 resides in a B cell super-enhancer, disrupting a conserved RELA-binding site•The rs539846 risk allele (A) reduces enhancer activity and RELA binding in CLL•rs539846-A confers lower BMF expression Kandaswamy et al. find that SNP rs539846 underlies the 15q15.1 chronic lymphocytic leukemia risk locus. Follow-up data demonstrate that rs539846 resides within a transcriptional enhancer and alters RELA binding at a conserved site. The rs539846-A risk allele results in reduced RELA-mediated enhancer activity and lower expression of BCL-2-modifying factor.
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.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.
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.
Author Catovsky, Daniel
Beà, Sílvia
Houlston, Richard S.
Salaverria, Itziar
Gutiérrez-Abril, Jesús
Speedy, Helen E.
Martín-Subero, José I.
Law, Philip J.
Martín-García, David
Puente, Xose S.
Studd, James B.
Allan, James M.
Kandaswamy, Radhika
López-Otín, Carlos
Sava, Georgina P.
Migliorini, Gabriele
Campo, Elías
AuthorAffiliation 3 Departament d’Anatomía Patològica, Microbiología i Farmacología, Universitat de Barcelona, 08036 Barcelona, Spain
1 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
4 Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain
6 Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK
5 Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK
7 Unitat de Hematología, Hospital Clínic, IDIBAPS, Universitat de Barcelona, 08036 Barcelona, Spain
2 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
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  organization: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
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Cites_doi 10.1038/ncomms10933
10.1182/blood.V82.6.1820.1820
10.1126/science.1062257
10.1038/sj.leu.2403202
10.1038/ng.219
10.1016/j.cell.2013.09.053
10.1016/j.imlet.2013.09.015
10.1056/NEJMoa1513257
10.1038/nature14962
10.1016/S0140-6736(07)61125-8
10.3324/haematol.2010.025338
10.1038/sj.leu.2403623
10.3324/haematol.2012.070201
10.1182/blood-2010-09-308205
10.1101/gr.3715005
10.1038/ng.2652
10.1038/sj.leu.2404467
10.1038/nature14666
10.1016/j.cell.2014.11.021
10.1016/B978-0-12-391938-0.00004-5
10.1182/blood-2007-10-116889
10.1038/nature11247
10.1038/ng.2843
10.1038/nature11632
10.1371/journal.pone.0107497
10.1101/gr.3577405
10.1093/imanum/drs019
10.1158/1535-7163.MCT-13-0058
10.1084/jem.20071658
10.1038/ng.510
10.1182/blood-2012-03-413591
10.1093/bioinformatics/bts163
10.1371/journal.pgen.1000529
10.1182/blood-2012-05-429282
10.4049/jimmunol.164.4.2200
10.1093/nar/gkr917
10.1038/nmeth.1906
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References Mackus, Kater, Grummels, Evers, Hooijbrink, Kramer, Castro, Kipps, van Lier, van Oers, Eldering (bib18) 2005; 19
Berndt, Skibola, Joseph, Camp, Nieters, Wang, Cozen, Monnereau, Wang, Kelly (bib2) 2013; 45
Hanada, Delia, Aiello, Stadtmauer, Reed (bib13) 1993; 82
Crowther-Swanepoel, Broderick, Di Bernardo, Dobbins, Torres, Mansouri, Ruiz-Ponte, Enjuanes, Rosenquist, Carracedo (bib7) 2010; 42
Puente, Beà, Valdés-Mas, Villamor, Gutiérrez-Abril, Martín-Subero, Munar, Rubio-Pérez, Jares, Aymerich (bib22) 2015; 526
Slager, Rabe, Achenbach, Vachon, Goldin, Strom, Lanasa, Spector, Rassenti, Leis (bib30) 2011; 117
Morales, Gutman, Lee, Boise (bib19) 2008; 111
Walter, Min, Huang, Crooks, Memari, McCarthy, Perry, Xu, Futema (bib33) 2015; 526
(bib9) 2012; 489
Slager, Skibola, Di Bernardo, Conde, Broderick, McDonnell, Goldin, Croft, Holroyd, Harris (bib31) 2012; 120
van de Werken, de Vree, Splinter, Holwerda, Klous, de Wit, de Laat (bib34) 2012
Di Bernardo, Crowther-Swanepoel, Broderick, Webb, Sellick, Wild, Sullivan, Vijayakrishnan, Wang, Pittman (bib8) 2008; 40
Billard (bib4) 2013; 12
Knight, Ruiz (bib16) 2013; 33
Scales, Jäger, Migliorini, Houlston, Henrion (bib26) 2014; 9
Berndt, Camp, Skibola, Vijai, Wang, Gu, Nieters, Kelly, Smedby, Monnereau (bib3) 2016; 7
Gonzalez, Else, Wren, Usai, Buhl, Parker, Oscier, Morgan, Catovsky (bib12) 2013; 98
Labi, Erlacher, Kiessling, Manzl, Frenzel, O’Reilly, Strasser, Villunger (bib17) 2008; 205
Rao, Huntley, Durand, Stamenova, Bochkov, Robinson, Sanborn, Machol, Omer, Lander, Aiden (bib24) 2014; 159
Ward, Kellis (bib37) 2012; 40
van Krieken, Langerak, Macintyre, Kneba, Hodges, Sanz, Morgan, Parreira, Molina, Cabeçadas (bib36) 2007; 21
Roberts, Davids, Pagel, Kahl, Puvvada, Gerecitano, Kipps, Anderson, Brown, Gressick (bib25) 2016; 374
Furman, Asgary, Mascarenhas, Liou, Schattner (bib11) 2000; 164
Speedy, Di Bernardo, Sava, Dyer, Holroyd, Wang, Sunter, Mansouri, Juliusson, Smedby (bib32) 2014; 46
Scarfò, Ghia (bib27) 2013; 155
Shabalin (bib28) 2012; 28
Oscier, Wade, Davis, Morilla, Best, Richards, Else, Matutes, Catovsky (bib20) 2010; 95
Hnisz, Abraham, Lee, Lau, Saint-André, Sigova, Hoke, Young (bib14) 2013; 155
Ernst, Kellis (bib10) 2012; 9
Puthalakath, Villunger, O’Reilly, Beaumont, Coultas, Cheney, Huang, Strasser (bib23) 2001; 293
Abecasis, Auton, Brooks, DePristo, Durbin, Handsaker, Kang, Marth, McVean (bib1) 2012; 491
Oscier, Rose-Zerilli, Winkelmann, Gonzalez de Castro, Gomez, Forster, Parker, Parker, Gardiner, Collins (bib21) 2013; 121
Catovsky, Richards, Matutes, Oscier, Dyer, Bezares, Pettitt, Hamblin, Milligan, Child (bib5) 2007; 370
Cooper, Stone, Asimenos, Green, Batzoglou, Sidow (bib6) 2005; 15
Siepel, Bejerano, Pedersen, Hinrichs, Hou, Rosenbloom, Clawson, Spieth, Hillier, Richards (bib29) 2005; 15
Howie, Donnelly, Marchini (bib15) 2009; 5
van Dongen, Langerak, Brüggemann, Evans, Hummel, Lavender, Delabesse, Davi, Schuuring, García-Sanz (bib35) 2003; 17
Hnisz (10.1016/j.celrep.2016.07.053_bib14) 2013; 155
Labi (10.1016/j.celrep.2016.07.053_bib17) 2008; 205
Gonzalez (10.1016/j.celrep.2016.07.053_bib12) 2013; 98
Knight (10.1016/j.celrep.2016.07.053_bib16) 2013; 33
Morales (10.1016/j.celrep.2016.07.053_bib19) 2008; 111
Slager (10.1016/j.celrep.2016.07.053_bib31) 2012; 120
van Dongen (10.1016/j.celrep.2016.07.053_bib35) 2003; 17
Ernst (10.1016/j.celrep.2016.07.053_bib10) 2012; 9
Cooper (10.1016/j.celrep.2016.07.053_bib6) 2005; 15
Oscier (10.1016/j.celrep.2016.07.053_bib20) 2010; 95
(10.1016/j.celrep.2016.07.053_bib9) 2012; 489
Furman (10.1016/j.celrep.2016.07.053_bib11) 2000; 164
Puente (10.1016/j.celrep.2016.07.053_bib22) 2015; 526
Mackus (10.1016/j.celrep.2016.07.053_bib18) 2005; 19
Slager (10.1016/j.celrep.2016.07.053_bib30) 2011; 117
van Krieken (10.1016/j.celrep.2016.07.053_bib36) 2007; 21
Abecasis (10.1016/j.celrep.2016.07.053_bib1) 2012; 491
Di Bernardo (10.1016/j.celrep.2016.07.053_bib8) 2008; 40
Hanada (10.1016/j.celrep.2016.07.053_bib13) 1993; 82
Scarfò (10.1016/j.celrep.2016.07.053_bib27) 2013; 155
Oscier (10.1016/j.celrep.2016.07.053_bib21) 2013; 121
Berndt (10.1016/j.celrep.2016.07.053_bib2) 2013; 45
Shabalin (10.1016/j.celrep.2016.07.053_bib28) 2012; 28
Puthalakath (10.1016/j.celrep.2016.07.053_bib23) 2001; 293
Howie (10.1016/j.celrep.2016.07.053_bib15) 2009; 5
Rao (10.1016/j.celrep.2016.07.053_bib24) 2014; 159
Speedy (10.1016/j.celrep.2016.07.053_bib32) 2014; 46
van de Werken (10.1016/j.celrep.2016.07.053_bib34) 2012
Crowther-Swanepoel (10.1016/j.celrep.2016.07.053_bib7) 2010; 42
Siepel (10.1016/j.celrep.2016.07.053_bib29) 2005; 15
Scales (10.1016/j.celrep.2016.07.053_bib26) 2014; 9
Berndt (10.1016/j.celrep.2016.07.053_bib3) 2016; 7
Roberts (10.1016/j.celrep.2016.07.053_bib25) 2016; 374
Ward (10.1016/j.celrep.2016.07.053_bib37) 2012; 40
Catovsky (10.1016/j.celrep.2016.07.053_bib5) 2007; 370
Billard (10.1016/j.celrep.2016.07.053_bib4) 2013; 12
Walter (10.1016/j.celrep.2016.07.053_bib33) 2015; 526
References_xml – volume: 15
  start-page: 901
  year: 2005
  end-page: 913
  ident: bib6
  article-title: Distribution and intensity of constraint in mammalian genomic sequence
  publication-title: Genome Res.
– start-page: 89
  year: 2012
  end-page: 112
  ident: bib34
  article-title: 4C technology: protocols and data analysis
  publication-title: Methods in Enzymology
– volume: 9
  start-page: e107497
  year: 2014
  ident: bib26
  article-title: visPIG--a web tool for producing multi-region, multi-track, multi-scale plots of genetic data
  publication-title: PLoS ONE
– volume: 155
  start-page: 36
  year: 2013
  end-page: 39
  ident: bib27
  article-title: Reprogramming cell death: BCL2 family inhibition in hematological malignancies
  publication-title: Immunol. Lett.
– volume: 5
  start-page: e1000529
  year: 2009
  ident: bib15
  article-title: A flexible and accurate genotype imputation method for the next generation of genome-wide association studies
  publication-title: PLoS Genet.
– volume: 489
  start-page: 57
  year: 2012
  end-page: 74
  ident: bib9
  article-title: An integrated encyclopedia of DNA elements in the human genome
  publication-title: Nature
– volume: 46
  start-page: 56
  year: 2014
  end-page: 60
  ident: bib32
  article-title: A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
– volume: 205
  start-page: 641
  year: 2008
  end-page: 655
  ident: bib17
  article-title: Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates γ irradiation-induced thymic lymphoma development
  publication-title: J. Exp. Med.
– volume: 42
  start-page: 132
  year: 2010
  end-page: 136
  ident: bib7
  article-title: Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk
  publication-title: Nat. Genet.
– volume: 19
  start-page: 427
  year: 2005
  end-page: 434
  ident: bib18
  article-title: Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation
  publication-title: Leukemia
– volume: 159
  start-page: 1665
  year: 2014
  end-page: 1680
  ident: bib24
  article-title: A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping
  publication-title: Cell
– volume: 120
  start-page: 843
  year: 2012
  end-page: 846
  ident: bib31
  article-title: Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia
  publication-title: Blood
– volume: 7
  start-page: 10933
  year: 2016
  ident: bib3
  article-title: Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  publication-title: Nat. Commun.
– volume: 82
  start-page: 1820
  year: 1993
  end-page: 1828
  ident: bib13
  article-title: bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia
  publication-title: Blood
– volume: 526
  start-page: 519
  year: 2015
  end-page: 524
  ident: bib22
  article-title: Non-coding recurrent mutations in chronic lymphocytic leukaemia
  publication-title: Nature
– volume: 12
  start-page: 1691
  year: 2013
  end-page: 1700
  ident: bib4
  article-title: BH3 mimetics: status of the field and new developments
  publication-title: Mol. Cancer Ther.
– volume: 370
  start-page: 230
  year: 2007
  end-page: 239
  ident: bib5
  article-title: Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial
  publication-title: Lancet
– volume: 155
  start-page: 934
  year: 2013
  end-page: 947
  ident: bib14
  article-title: Super-enhancers in the control of cell identity and disease
  publication-title: Cell
– volume: 17
  start-page: 2257
  year: 2003
  end-page: 2317
  ident: bib35
  article-title: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936
  publication-title: Leukemia
– volume: 164
  start-page: 2200
  year: 2000
  end-page: 2206
  ident: bib11
  article-title: Modulation of NF-κ B activity and apoptosis in chronic lymphocytic leukemia B cells
  publication-title: J. Immunol.
– volume: 374
  start-page: 311
  year: 2016
  end-page: 322
  ident: bib25
  article-title: Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia
  publication-title: N. Engl. J. Med.
– volume: 33
  start-page: 1029
  year: 2013
  end-page: 1047
  ident: bib16
  article-title: A fast algorithm for matrix balancing
  publication-title: IMA J. Numer. Anal.
– volume: 15
  start-page: 1034
  year: 2005
  end-page: 1050
  ident: bib29
  article-title: Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
  publication-title: Genome Res.
– volume: 21
  start-page: 201
  year: 2007
  end-page: 206
  ident: bib36
  article-title: Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936
  publication-title: Leukemia
– volume: 491
  start-page: 56
  year: 2012
  end-page: 65
  ident: bib1
  article-title: An integrated map of genetic variation from 1,092 human genomes
  publication-title: Nature
– volume: 95
  start-page: 1705
  year: 2010
  end-page: 1712
  ident: bib20
  article-title: Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation
  publication-title: Haematologica
– volume: 293
  start-page: 1829
  year: 2001
  end-page: 1832
  ident: bib23
  article-title: Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis
  publication-title: Science
– volume: 121
  start-page: 468
  year: 2013
  end-page: 475
  ident: bib21
  article-title: The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial
  publication-title: Blood
– volume: 9
  start-page: 215
  year: 2012
  end-page: 216
  ident: bib10
  article-title: ChromHMM: automating chromatin-state discovery and characterization
  publication-title: Nat. Methods
– volume: 117
  start-page: 1911
  year: 2011
  end-page: 1916
  ident: bib30
  article-title: Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL
  publication-title: Blood
– volume: 45
  start-page: 868
  year: 2013
  end-page: 876
  ident: bib2
  article-title: Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
– volume: 40
  start-page: D930
  year: 2012
  end-page: D934
  ident: bib37
  article-title: HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants
  publication-title: Nucleic Acids Res.
– volume: 111
  start-page: 5152
  year: 2008
  end-page: 5162
  ident: bib19
  article-title: BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma
  publication-title: Blood
– volume: 526
  start-page: 82
  year: 2015
  end-page: 90
  ident: bib33
  article-title: The UK10K project identifies rare variants in health and disease
  publication-title: Nature
– volume: 28
  start-page: 1353
  year: 2012
  end-page: 1358
  ident: bib28
  article-title: Matrix eQTL: ultra fast eQTL analysis via large matrix operations
  publication-title: Bioinformatics
– volume: 40
  start-page: 1204
  year: 2008
  end-page: 1210
  ident: bib8
  article-title: A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
– volume: 98
  start-page: 274
  year: 2013
  end-page: 278
  ident: bib12
  article-title: CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes
  publication-title: Haematologica
– volume: 7
  start-page: 10933
  year: 2016
  ident: 10.1016/j.celrep.2016.07.053_bib3
  article-title: Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms10933
– volume: 82
  start-page: 1820
  year: 1993
  ident: 10.1016/j.celrep.2016.07.053_bib13
  article-title: bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia
  publication-title: Blood
  doi: 10.1182/blood.V82.6.1820.1820
– volume: 293
  start-page: 1829
  year: 2001
  ident: 10.1016/j.celrep.2016.07.053_bib23
  article-title: Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis
  publication-title: Science
  doi: 10.1126/science.1062257
– volume: 17
  start-page: 2257
  year: 2003
  ident: 10.1016/j.celrep.2016.07.053_bib35
  article-title: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936
  publication-title: Leukemia
  doi: 10.1038/sj.leu.2403202
– volume: 40
  start-page: 1204
  year: 2008
  ident: 10.1016/j.celrep.2016.07.053_bib8
  article-title: A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
  doi: 10.1038/ng.219
– volume: 155
  start-page: 934
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib14
  article-title: Super-enhancers in the control of cell identity and disease
  publication-title: Cell
  doi: 10.1016/j.cell.2013.09.053
– volume: 155
  start-page: 36
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib27
  article-title: Reprogramming cell death: BCL2 family inhibition in hematological malignancies
  publication-title: Immunol. Lett.
  doi: 10.1016/j.imlet.2013.09.015
– volume: 374
  start-page: 311
  year: 2016
  ident: 10.1016/j.celrep.2016.07.053_bib25
  article-title: Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1513257
– volume: 526
  start-page: 82
  year: 2015
  ident: 10.1016/j.celrep.2016.07.053_bib33
  article-title: The UK10K project identifies rare variants in health and disease
  publication-title: Nature
  doi: 10.1038/nature14962
– volume: 370
  start-page: 230
  year: 2007
  ident: 10.1016/j.celrep.2016.07.053_bib5
  article-title: Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(07)61125-8
– volume: 95
  start-page: 1705
  year: 2010
  ident: 10.1016/j.celrep.2016.07.053_bib20
  article-title: Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation
  publication-title: Haematologica
  doi: 10.3324/haematol.2010.025338
– volume: 19
  start-page: 427
  year: 2005
  ident: 10.1016/j.celrep.2016.07.053_bib18
  article-title: Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation
  publication-title: Leukemia
  doi: 10.1038/sj.leu.2403623
– volume: 98
  start-page: 274
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib12
  article-title: CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes
  publication-title: Haematologica
  doi: 10.3324/haematol.2012.070201
– volume: 117
  start-page: 1911
  year: 2011
  ident: 10.1016/j.celrep.2016.07.053_bib30
  article-title: Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL
  publication-title: Blood
  doi: 10.1182/blood-2010-09-308205
– volume: 15
  start-page: 1034
  year: 2005
  ident: 10.1016/j.celrep.2016.07.053_bib29
  article-title: Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
  publication-title: Genome Res.
  doi: 10.1101/gr.3715005
– volume: 45
  start-page: 868
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib2
  article-title: Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
  doi: 10.1038/ng.2652
– volume: 21
  start-page: 201
  year: 2007
  ident: 10.1016/j.celrep.2016.07.053_bib36
  article-title: Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936
  publication-title: Leukemia
  doi: 10.1038/sj.leu.2404467
– volume: 526
  start-page: 519
  year: 2015
  ident: 10.1016/j.celrep.2016.07.053_bib22
  article-title: Non-coding recurrent mutations in chronic lymphocytic leukaemia
  publication-title: Nature
  doi: 10.1038/nature14666
– volume: 159
  start-page: 1665
  year: 2014
  ident: 10.1016/j.celrep.2016.07.053_bib24
  article-title: A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping
  publication-title: Cell
  doi: 10.1016/j.cell.2014.11.021
– start-page: 89
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib34
  article-title: 4C technology: protocols and data analysis
  doi: 10.1016/B978-0-12-391938-0.00004-5
– volume: 111
  start-page: 5152
  year: 2008
  ident: 10.1016/j.celrep.2016.07.053_bib19
  article-title: BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma
  publication-title: Blood
  doi: 10.1182/blood-2007-10-116889
– volume: 489
  start-page: 57
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib9
  article-title: An integrated encyclopedia of DNA elements in the human genome
  publication-title: Nature
  doi: 10.1038/nature11247
– volume: 46
  start-page: 56
  year: 2014
  ident: 10.1016/j.celrep.2016.07.053_bib32
  article-title: A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia
  publication-title: Nat. Genet.
  doi: 10.1038/ng.2843
– volume: 491
  start-page: 56
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib1
  article-title: An integrated map of genetic variation from 1,092 human genomes
  publication-title: Nature
  doi: 10.1038/nature11632
– volume: 9
  start-page: e107497
  year: 2014
  ident: 10.1016/j.celrep.2016.07.053_bib26
  article-title: visPIG--a web tool for producing multi-region, multi-track, multi-scale plots of genetic data
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0107497
– volume: 15
  start-page: 901
  year: 2005
  ident: 10.1016/j.celrep.2016.07.053_bib6
  article-title: Distribution and intensity of constraint in mammalian genomic sequence
  publication-title: Genome Res.
  doi: 10.1101/gr.3577405
– volume: 33
  start-page: 1029
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib16
  article-title: A fast algorithm for matrix balancing
  publication-title: IMA J. Numer. Anal.
  doi: 10.1093/imanum/drs019
– volume: 12
  start-page: 1691
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib4
  article-title: BH3 mimetics: status of the field and new developments
  publication-title: Mol. Cancer Ther.
  doi: 10.1158/1535-7163.MCT-13-0058
– volume: 205
  start-page: 641
  year: 2008
  ident: 10.1016/j.celrep.2016.07.053_bib17
  article-title: Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates γ irradiation-induced thymic lymphoma development
  publication-title: J. Exp. Med.
  doi: 10.1084/jem.20071658
– volume: 42
  start-page: 132
  year: 2010
  ident: 10.1016/j.celrep.2016.07.053_bib7
  article-title: Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk
  publication-title: Nat. Genet.
  doi: 10.1038/ng.510
– volume: 120
  start-page: 843
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib31
  article-title: Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia
  publication-title: Blood
  doi: 10.1182/blood-2012-03-413591
– volume: 28
  start-page: 1353
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib28
  article-title: Matrix eQTL: ultra fast eQTL analysis via large matrix operations
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/bts163
– volume: 5
  start-page: e1000529
  year: 2009
  ident: 10.1016/j.celrep.2016.07.053_bib15
  article-title: A flexible and accurate genotype imputation method for the next generation of genome-wide association studies
  publication-title: PLoS Genet.
  doi: 10.1371/journal.pgen.1000529
– volume: 121
  start-page: 468
  year: 2013
  ident: 10.1016/j.celrep.2016.07.053_bib21
  article-title: The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial
  publication-title: Blood
  doi: 10.1182/blood-2012-05-429282
– volume: 164
  start-page: 2200
  year: 2000
  ident: 10.1016/j.celrep.2016.07.053_bib11
  article-title: Modulation of NF-κ B activity and apoptosis in chronic lymphocytic leukemia B cells
  publication-title: J. Immunol.
  doi: 10.4049/jimmunol.164.4.2200
– volume: 40
  start-page: D930
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib37
  article-title: HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkr917
– volume: 9
  start-page: 215
  year: 2012
  ident: 10.1016/j.celrep.2016.07.053_bib10
  article-title: ChromHMM: automating chromatin-state discovery and characterization
  publication-title: Nat. Methods
  doi: 10.1038/nmeth.1906
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Snippet Chronic lymphocytic leukemia (CLL) is an adult B cell malignancy. Genome-wide association studies show that variation at 15q15.1 influences CLL risk. We...
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SubjectTerms Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Alleles
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
Binding Sites
Cell Line, Tumor
Chromatin - chemistry
Chromatin - metabolism
Chromosome Mapping
Chromosomes, Human, Pair 15
Enhancer Elements, Genetic
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Histones - genetics
Histones - metabolism
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Odds Ratio
Polymorphism, Single Nucleotide
Protein Binding
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Risk
Transcription Factor RelA - genetics
Transcription Factor RelA - metabolism
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Title Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism
URI https://dx.doi.org/10.1016/j.celrep.2016.07.053
https://www.ncbi.nlm.nih.gov/pubmed/27524613
https://www.proquest.com/docview/1814664414
https://pubmed.ncbi.nlm.nih.gov/PMC4999417
https://doaj.org/article/e91cfff18d49416982e8980133481082
Volume 16
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