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

Cell Reports

Volumn 16, Issue 8, 2016, Pages 2061-2067

  Kandaswamy, Radhika ^a   Sava, Georgina P ^a   Speedy, Helen E ^a   Beà, Sílvia ^b   Martín Subero, José I ^b,c   Studd, James B ^a   Migliorini, Gabriele ^a   Law, Philip J ^a   Puente, Xose S ^d   Martín García, David ^b   Salaverria, Itziar ^b   Gutiérrez Abril, Jesús ^d   López Otín, Carlos ^d   Catovsky, Daniel ^a   Allan, James M ^e   Campo, Elías ^c   Houlston, Richard S ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

^d DEPARTAMENTO DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR   (Spain)

^e NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN HEAVY CHAIN; NOTCH1 RECEPTOR; TRANSCRIPTION FACTOR RELA; BCL2 PROTEIN, HUMAN; BMF PROTEIN, HUMAN; HISTONE; PROTEIN BCL 2; PROTEIN BINDING; RELA PROTEIN, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ARTICLE; BINDING SITE; BMF GENE; CHROMATIN IMMUNOPRECIPITATION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; GENE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC CONSERVATION; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENOTYPE; HOMOZYGOSITY; HUMAN; HUMAN CELL; INTRON; PRIORITY JOURNAL; PROTEIN DNA INTERACTION; RNA SEQUENCE; SINGLE NUCLEOTIDE POLYMORPHISM; ALLELE; B LYMPHOCYTE; CHEMISTRY; CHROMATIN; CHROMOSOMAL MAPPING; CHROMOSOME 15; ENHANCER REGION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; METABOLISM; ODDS RATIO; PATHOLOGY; RISK; TUMOR CELL LINE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ALLELES; B-LYMPHOCYTES; BINDING SITES; CELL LINE, TUMOR; CHROMATIN; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 15; ENHANCER ELEMENTS, GENETIC; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HISTONES; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; ODDS RATIO; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-BCL-2; RISK; TRANSCRIPTION FACTOR RELA;

EID: 84981736573     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.07.053     Document Type: Article

References (37)

1. Abecasis, G.R., Auton, A., Brooks, L.D., DePristo, M.A., Durbin, R.M., Handsaker, R.E., Kang, H.M., Marth, G.T., McVean, G.A., 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 491 (2012), 56–65.
2. Berndt, S.I., Skibola, C.F., Joseph, V., Camp, N.J., Nieters, A., Wang, Z., Cozen, W., Monnereau, A., Wang, S.S., Kelly, R.S., et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat. Genet. 45 (2013), 868–876.
3. Berndt, S.I., Camp, N.J., Skibola, C.F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R.S., Smedby, K.E., Monnereau, A., et al. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat. Commun., 7, 2016, 10933.
4. Billard, C., BH3 mimetics: status of the field and new developments. Mol. Cancer Ther. 12 (2013), 1691–1700.
5. Catovsky, D., Richards, S., Matutes, E., Oscier, D., Dyer, M.J., Bezares, R.F., Pettitt, A.R., Hamblin, T., Milligan, D.W., Child, J.A., et al. UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group, NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet 370 (2007), 230–239.
6. Cooper, G.M., Stone, E.A., Asimenos, G., Green, E.D., Batzoglou, S., Sidow, A., NISC Comparative Sequencing Program. Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 15 (2005), 901–913.
7. Crowther-Swanepoel, D., Broderick, P., Di Bernardo, M.C., Dobbins, S.E., Torres, M., Mansouri, M., Ruiz-Ponte, C., Enjuanes, A., Rosenquist, R., Carracedo, A., et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat. Genet. 42 (2010), 132–136.
8. Di Bernardo, M.C., Crowther-Swanepoel, D., Broderick, P., Webb, E., Sellick, G., Wild, R., Sullivan, K., Vijayakrishnan, J., Wang, Y., Pittman, A.M., et al. A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nat. Genet. 40 (2008), 1204–1210.
9. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489 (2012), 57–74.
10. Ernst, J., Kellis, M., ChromHMM: automating chromatin-state discovery and characterization. Nat. Methods 9 (2012), 215–216.
11. Furman, R.R., Asgary, Z., Mascarenhas, J.O., Liou, H.-C., Schattner, E.J., Modulation of NF-κ B activity and apoptosis in chronic lymphocytic leukemia B cells. J. Immunol. 164 (2000), 2200–2206.
12. Gonzalez, D., Else, M., Wren, D., Usai, M., Buhl, A.M., Parker, A., Oscier, D., Morgan, G., Catovsky, D., CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes. Haematologica 98 (2013), 274–278.
13. Hanada, M., Delia, D., Aiello, A., Stadtmauer, E., Reed, J.C., bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 82 (1993), 1820–1828.
14. Hnisz, D., Abraham, B.J., Lee, T.I., Lau, A., Saint-André, V., Sigova, A.A., Hoke, H.A., Young, R.A., Super-enhancers in the control of cell identity and disease. Cell 155 (2013), 934–947.
15. Howie, B.N., Donnelly, P., Marchini, J., A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet., 5, 2009, e1000529.
16. Knight, P.A., Ruiz, D., A fast algorithm for matrix balancing. IMA J. Numer. Anal. 33 (2013), 1029–1047.
17. Labi, V., Erlacher, M., Kiessling, S., Manzl, C., Frenzel, A., O'Reilly, L., Strasser, A., Villunger, A., Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates γ irradiation-induced thymic lymphoma development. J. Exp. Med. 205 (2008), 641–655.
18. Mackus, W.J.M., Kater, A.P., Grummels, A., Evers, L.M., Hooijbrink, B., Kramer, M.H.H., Castro, J.E., Kipps, T.J., van Lier, R.A.W., van Oers, M.H.J., Eldering, E., Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia 19 (2005), 427–434.
19. Morales, A.A., Gutman, D., Lee, K.P., Boise, L.H., BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma. Blood 111 (2008), 5152–5162.
20. Oscier, D., Wade, R., Davis, Z., Morilla, A., Best, G., Richards, S., Else, M., Matutes, E., Catovsky, D., Chronic Lymphocytic Leukaemia Working Group, UK National Cancer Research Institute. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation. Haematologica 95 (2010), 1705–1712.
21. Oscier, D.G., Rose-Zerilli, M.J., Winkelmann, N., Gonzalez de Castro, D., Gomez, B., Forster, J., Parker, H., Parker, A., Gardiner, A., Collins, A., et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood 121 (2013), 468–475.
22. Puente, X.S., Beà, S., Valdés-Mas, R., Villamor, N., Gutiérrez-Abril, J., Martín-Subero, J.I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature 526 (2015), 519–524 advance online publication.
23. Puthalakath, H., Villunger, A., O'Reilly, L.A., Beaumont, J.G., Coultas, L., Cheney, R.E., Huang, D.C.S., Strasser, A., Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293 (2001), 1829–1832.
24. Rao, S.S., Huntley, M.H., Durand, N.C., Stamenova, E.K., Bochkov, I.D., Robinson, J.T., Sanborn, A.L., Machol, I., Omer, A.D., Lander, E.S., Aiden, E.L., A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159 (2014), 1665–1680.
25. Roberts, A.W., Davids, M.S., Pagel, J.M., Kahl, B.S., Puvvada, S.D., Gerecitano, J.F., Kipps, T.J., Anderson, M.A., Brown, J.R., Gressick, L., et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374 (2016), 311–322.
26. Scales, M., Jäger, R., Migliorini, G., Houlston, R.S., Henrion, M.Y., visPIG—a web tool for producing multi-region, multi-track, multi-scale plots of genetic data. PLoS ONE, 9, 2014, e107497.
27. Scarfò, L., Ghia, P., Reprogramming cell death: BCL2 family inhibition in hematological malignancies. Immunol. Lett. 155 (2013), 36–39.
28. Shabalin, A.A., Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28 (2012), 1353–1358.
29. Siepel, A., Bejerano, G., Pedersen, J.S., Hinrichs, A.S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L.W., Richards, S., et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15 (2005), 1034–1050.
30. Slager, S.L., Rabe, K.G., Achenbach, S.J., Vachon, C.M., Goldin, L.R., Strom, S.S., Lanasa, M.C., Spector, L.G., Rassenti, L.Z., Leis, J.F., et al. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood 117 (2011), 1911–1916.
31. Slager, S.L., Skibola, C.F., Di Bernardo, M.C., Conde, L., Broderick, P., McDonnell, S.K., Goldin, L.R., Croft, N., Holroyd, A., Harris, S., et al. Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia. Blood 120 (2012), 843–846.
32. Speedy, H.E., Di Bernardo, M.C., Sava, G.P., Dyer, M.J., Holroyd, A., Wang, Y., Sunter, N.J., Mansouri, L., Juliusson, G., Smedby, K.E., et al. A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nat. Genet. 46 (2014), 56–60.
33. UK10K Consortium, Walter, K., Min, J.L., Huang, J., Crooks, L., Memari, Y., McCarthy, S., Perry, J.R., Xu, C., Futema, M., et al. The UK10K project identifies rare variants in health and disease. Nature 526 (2015), 82–90.
34. van de Werken, H.J.G., de Vree, P.J.P., Splinter, E., Holwerda, S.J.B., Klous, P., de Wit, E., de Laat, W., 4C technology: protocols and data analysis. Carl, W., Allis, C.D., (eds.) Methods in Enzymology, 2012, Academic Press, 89–112.
35. van Dongen, J.J., Langerak, A.W., Brüggemann, M., Evans, P.A., Hummel, M., Lavender, F.L., Delabesse, E., Davi, F., Schuuring, E., García-Sanz, R., et al. 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. Leukemia 17 (2003), 2257–2317.
36. van Krieken, J.H., Langerak, A.W., Macintyre, E.A., Kneba, M., Hodges, E., Sanz, R.G., Morgan, G.J., Parreira, A., Molina, T.J., Cabeçadas, J., et al. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21 (2007), 201–206.
37. Ward, L.D., Kellis, M., HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40 (2012), D930–D934.