Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target

Oncotarget

Volumn 7, Issue 6, 2016, Pages 6809-6823

  Agarwal, Prasoon ^a   Alzrigat, Mohammad ^a   Párraga, Alba Atienza ^a   Enroth, Stefan ^a   Singh, Umashankar ^b   Ungerstedt, Johanna ^c   Österborg, Anders ^d   Brown, Peter J ^e   Ma, Anqi ^f   Jin, Jian ^f   Nilsson, Kenneth ^a   Öberg, Fredrik ^a   Kalushkova, Antonia ^a   Jernberg Wiklund, Helena ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b INDIAN INSTITUTE OF TECHNOLOGY GANDHINAGAR   (India)

^c KAROLINSKA INSTITUTE   (Sweden)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^e UNIVERSITY OF TORONTO   (Canada)

^f MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

EZH2; H3K27me3; Multiple myeloma; Polycomb; UNC1999

Indexed keywords

GSK 343; HISTONE H3; LYSINE; METHYLTRANSFERASE; PROTEIN INHIBITOR; TRANSCRIPTION FACTOR EZH2; UNC 1999; UNCLASSIFIED DRUG; CHROMATIN; ENZYME INHIBITOR; EZH2 PROTEIN, HUMAN; HISTONE; POLYCOMB GROUP PROTEIN;

APOPTOSIS; ARTICLE; CANCER SURVIVAL; CELL SURVIVAL; CELL VIABILITY; COHORT ANALYSIS; CONTROLLED STUDY; ENZYME ACTIVITY; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE SEQUENCE; GENE SILENCING; H3K27ME3 GENE; HISTONE METHYLATION; HUMAN; HUMAN CELL; IN VITRO STUDY; MULTIPLE MYELOMA; ONCOGENE; PLASMA CELL; SEQUENCE ANALYSIS; ANTAGONISTS AND INHIBITORS; CHROMATIN; DOWN REGULATION; GENETICS; METABOLISM; METHYLATION; MOLECULARLY TARGETED THERAPY;

CHROMATIN; DOWN-REGULATION; ENHANCER OF ZESTE HOMOLOG 2 PROTEIN; ENZYME INHIBITORS; GENE EXPRESSION PROFILING; HISTONES; HUMANS; LYSINE; METHYLATION; MOLECULAR TARGETED THERAPY; MULTIPLE MYELOMA; POLYCOMB-GROUP PROTEINS;

EID: 84981186342     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6843     Document Type: Article

References (67)

1. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998; 91:3-21.
2. Chesi M, Bergsagel PL. Many multiple myelomas: making more of the molecular mayhem. Hematology Am Soc Hematol Educ Program. 2011; 2011:344-353.
3. Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002; 2:175-187.
4. Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, Mirabella F, Lopez-Corral L, Humphray S, Murray L, Ross M, Bentley D, Gutierrez NC, Garcia-Sanz R, San Miguel J, Davies FE, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia. 2014; 28:384-390.
5. Keats JJ, Chesi M, Egan JB, Garbitt VM, Palmer SE, Braggio E, Van Wier S, Blackburn PR, Baker AS, Dispenzieri A, Kumar S, Rajkumar SV, Carpten JD, Barrett M, Fonseca R, Stewart AK, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012; 120:1067-1076.
6. Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, Sougnez C, Knoechel B, Gould J, Saksena G, Cibulskis K, McKenna A, Chapman MA, Straussman R, Levy J, Perkins LM, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer cell. 2014; 25:91-101.
7. Bolli N, Avet-Loiseau H, Wedge DC, Van Loo P, Alexandrov LB, Martincorena I, Dawson KJ, Iorio F, Nik-Zainal S, Bignell GR, Hinton JW, Li Y, Tubio JM, McLaren S, S OM, Butler AP, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014; 5:2997.
8. Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. Journal of clinical oncology. 2005; 23:6333-6338.
9. Dimopoulos K, Gimsing P, Gronbaek K. The role of epigenetics in the biology of multiple myeloma. Blood cancer journal. 2014; 4:e207.
10. Keats JJ, Reiman T, Belch AR, Pilarski LM. Ten years and counting: so what do we know about t(4;14)(p16;q32) multiple myeloma. Leuk Lymphoma. 2006; 47:2289-2300.
11. Jenuwein T, Laible G, Dorn R, Reuter G. SET domain proteins modulate chromatin domains in eu-and heterochromatin. Cell Mol Life Sci. 1998; 54:80-93.
12. Martinez-Garcia E, Popovic R, Min DJ, Sweet SM, Thomas PM, Zamdborg L, Heffner A, Will C, Lamy L, Staudt LM, Levens DL, Kelleher NL, Licht JD. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood. 2011; 117:211-220.
13. Popovic R, Martinez-Garcia E, Giannopoulou EG, Zhang Q, Zhang Q, Ezponda T, Shah MY, Zheng Y, Will CM, Small EC, Hua Y, Bulic M, Jiang Y, et al. Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation. PLoS Genet. 2014; 10:e1004566. PMID:25188243.
14. van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C, Edkins S, Hardy C, O'Meara S, Teague J, Butler A, Hinton J, Latimer C, Andrews J, Barthorpe S, Beare D, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009; 41:521-523.
15. Kalushkova A, Fryknas M, Lemaire M, Fristedt C, Agarwal P, Eriksson M, Deleu S, Atadja P, Osterborg A, Nilsson K, Vanderkerken K, Oberg F, Jernberg-Wiklund H. Polycomb target genes are silenced in multiple myeloma. PLoS One. 2010; 5:e11483.
16. Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011; 469:343-349.
17. Simon JA, Kingston RE. Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol Cell. 2013; 49:808-824.
18. Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L, Mohammad HP, Chen W, Daniel VC, Yu W, Berman DM, Jenuwein T, Pruitt K, Sharkis SJ, Watkins DN, Herman JG, et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature genetics. 2007; 39:237-242.
19. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature genetics. 2007; 39:232-236.
20. Chase A, Cross NC. Aberrations of EZH2 in cancer. Clin Cancer Res. 2011; 17:2613-2618.
21. Melnick A. Epigenetic therapy leaps ahead with specific targeting of EZH2. Cancer cell. 2012; 22:569-570.
22. Croonquist PA, Van Ness B. The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype. Oncogene. 2005; 24:6269-6280.
23. Young MD, Willson TA, Wakefield MJ, Trounson E, Hilton DJ, Blewitt ME, Oshlack A, Majewski IJ. ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity. Nucleic Acids Res. 2011; 39:7415-7427.
24. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007; 448:553-560.
25. Ruthenburg AJ, Allis CD, Wysocka J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell. 2007; 25:15-30.
26. Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P, Varambally S, Ghosh D, Chinnaiyan AM. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007; 9:166-180.
27. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 2006; 20:1123-1136.
28. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, Koseki H, Fuchikami T, Abe K, Murray HL, Zucker JP, Yuan B, et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006; 125:301-313.
29. Agnelli L, Mosca L, Fabris S, Lionetti M, Andronache A, Kwee I, Todoerti K, Verdelli D, Battaglia C, Bertoni F, Deliliers GL, Neri A. A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect. Genes Chromosomes Cancer. 2009; 48:603-614.
30. Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S, Epstein J, Yaccoby S, Sawyer J, Burington B, Anaissie E, Hollmig K, Pineda-Roman M, Tricot G, van Rhee F, Walker R, et al. The molecular classification of multiple myeloma. Blood. 2006; 108:2020-2028.
31. Mulligan G, Mitsiades C, Bryant B, Zhan F, Chng WJ, Roels S, Koenig E, Fergus A, Huang Y, Richardson P, Trepicchio WL, Broyl A, Sonneveld P, Shaughnessy JD, Jr., Bergsagel PL, Schenkein D, et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood. 2007; 109:3177-3188.
32. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011; 471:467-472.
33. Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, et al. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS chemical biology. 2013; 8:1324-1334.
34. Verma SK, Tian X, LaFrance LV, Duquenne C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA, Graves AP, Scherzer DA, Shu A, Thompson C, Ott HM, Aller GS, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS medicinal chemistry letters. 2012; 3:1091-1096.
35. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A, 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012; 492:108-112.
36. Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao Y, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, Waters NJ, Smith JJ, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Molecular cancer therapeutics. 2014; 13:842-854.
37. Fan F, Vallet S, Sattler M, Tonon G, Bashari MH, Bakiri L, Goldschmidt H, Wagner EF, Jaeger D, Podar K. The AP-1 Transcription Factor JunB Promotes Multiple Myeloma (MM) Cell Proliferation, Survival and Drug Resistance in the Bone Marrow Microenvironment. Blood. 2014; 124:3446-3446.
38. Shaffer AL, Lin KI, Kuo TC, Yu X, Hurt EM, Rosenwald A, Giltnane JM, Yang L, Zhao H, Calame K, Staudt LM. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity. 2002; 17:51-62.
39. Diaz-Agustin B, Escribano L, Bravo P, Herrero S, Nunez R, Navalon R, Navarro L, Torrelo A, Cantalapiedra A, Del Castillo L, Villarrubia J, Navarro JL, San Miguel JF, Orfao A. The CD69 early activation molecule is overexpressed in human bone marrow mast cells from adults with indolent systemic mast cell disease. British journal of haematology. 1999; 106:400-405.
40. Buda G, Carulli G, Orciuolo E, Sammuri P, Campa D, Galimberti S, Petrini M. CD69, a New Potential Clinical Marker in Multiple Myeloma. Blood. 2014; 124:2027-2027.
41. Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, Friend D, Grusby MJ, Alt F, Glimcher LH. Plasma cell differentiation requires the transcription factor XBP-1. Nature. 2001; 412:300-307.
42. Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, et al. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer cell. 2007; 11:349-360.
43. Brioli A, Melchor L, Walker BA, Davies FE, Morgan GJ. Biology and treatment of myeloma. Clin Lymphoma Myeloma Leuk. 2014; 14:S65-70.
44. Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005; 23:6333-6338.
45. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nature genetics. 2008; 40:499-507.
46. Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell. 2004; 118:409-418.
47. Vicente-Duenas C, Romero-Camarero I, Gonzalez-Herrero I, Alonso-Escudero E, Abollo-Jimenez F, Jiang X, Gutierrez NC, Orfao A, Marin N, Villar LM, Criado MC, Pintado B, Flores T, Alonso-Lopez D, De Las Rivas J, Jimenez R, et al. A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors. EMBO J. 2012; 31:3704-3717.
48. Zhan F, Barlogie B, Arzoumanian V, Huang Y, Williams DR, Hollmig K, Pineda-Roman M, Tricot G, van Rhee F, Zangari M, Dhodapkar M, Shaughnessy JD, Jr. Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. Blood. 2007; 109:1692-1700.
49. Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, van Rhee F, Fassas A, Crowley J, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood. 2002; 99:1745-1757.
50. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, et al. International staging system for multiple myeloma. Journal of clinical oncology. 2005; 23:3412-3420.
51. Beguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, Rosen M, Shen H, Yang SN, Wang L, Ezponda T, Martinez-Garcia E, Zhang H, Zheng Y, Verma SK, McCabe MT, Ott HM, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer cell. 2013; 23:677-692.
52. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nature genetics. 2010; 42:181-185.
53. Majer CR, Jin L, Scott MP, Knutson SK, Kuntz KW, Keilhack H, Smith JJ, Moyer MP, Richon VM, Copeland RA, Wigle TJ. A687V EZH2 is a gain-of-function mutation found in lymphoma patients. FEBS letters. 2012; 586:3448-3451.
54. Sneeringer CJ, Scott MP, Kuntz KW, Knutson SK, Pollock RM, Richon VM, Copeland RA. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci U S A. 2010; 107:20980-20985.
55. Campbell JE, Kuntz KW, Knutson SK, Warholic NM, Keilhack H, Wigle TJ, Raimondi A, Klaus CR, Rioux N, Yokoi A, Kawano S, Minoshima Y, Choi HW, Porter Scott M, Waters NJ, Smith JJ, et al. EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity. ACS medicinal chemistry letters. 2015; 6:491-495.
56. Oancea M, Mani A, Hussein MA, Almasan A. Apoptosis of multiple myeloma. International journal of hematology. 2004; 80:224-231.
57. Chauhan D, Anderson KC. Apoptosis in multiple myeloma: therapeutic implications. Apoptosis. 2001; 6:47-55.
58. Zhou Y, Liu X, Xu L, Hunter ZR, Cao Y, Yang G, Carrasco R, Treon SP. Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenstrom macroglobulinaemia. British journal of haematology. 2014; 166:677-689.
59. Florio M, Hernandez MC, Yang H, Shu HK, Cleveland JL, Israel MA. Id2 promotes apoptosis by a novel mechanism independent of dimerization to basic helix-loop-helix factors. Molecular and cellular biology. 1998; 18:5435-5444.
60. Yokota Y, Mori S. Role of Id family proteins in growth control. Journal of cellular physiology. 2002; 190:21-28.
61. Ruzinova MB, Benezra R. Id proteins in development, cell cycle and cancer. Trends in cell biology. 2003; 13:410-418.
62. Xiang Z, Cutler AJ, Brownlie RJ, Fairfax K, Lawlor KE, Severinson E, Walker EU, Manz RA, Tarlinton DM, Smith KG. FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Nature immunology. 2007; 8:419-429.
63. Jernberg-Wiklund H, Nilsson K. (2002). Multiple Myeloma Cell Lines. In: Masters JW, Palsson B, eds. Human Cell Culture: Springer Netherlands), pp. 81-155.
64. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, Liu XS. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9:R137.
65. Salmon-Divon M, Dvinge H, Tammoja K, Bertone P. PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci. BMC Bioinformatics. 2010; 11:415.
66. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26:841-842.
67. Oliveros JC. (2007-2015). Venny. An interactive tool for comparing lists with Venn's diagrams.