Epigenetics in multiple myeloma: From mechanisms to therapy

被引:60
作者
Alzrigat, Mohammad [1 ]
Parraga, Alba Atienza [1 ]
Jernberg-Wiklund, Helena [1 ]
机构
[1] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Sci Life Lab, SE-75185 Uppsala, Sweden
基金
瑞典研究理事会;
关键词
Multiple myeloma; Epigenetics; Epigenetic therapy; TUMOR-SUPPRESSOR GENES; LONG NONCODING RNAS; HISTONE DEACETYLASE INHIBITORS; GROWTH-FACTOR RECEPTOR-3; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; DNA-METHYLATION; POOR-PROGNOSIS; IN-VIVO; DRUG-RESISTANCE;
D O I
10.1016/j.semcancer.2017.09.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma (MM) is a tumor of antibody producing plasmablasts/plasma cells that resides within the bone marrow (BM). In addition to the well-established role of genetic lesions and tumor-microenvironment interactions in the development of MM, deregulated epigenetic mechanisms are emerging as important in MM pathogenesis. Recently, MM sequencing and expression projects have revealed that mutations and copy number variations as well as deregulation in the expression of epigenetic modifiers are characteristic features of MM. In the past decade, several studies have suggested epigenetic mechanisms via DNA methylation, histone modifications and non-coding RNAs as important contributing factors in MM with impacts on disease initiation, progression, clonal heterogeneity and response to treatment. Herein we review the present view and knowledge that has accumulated over the past decades on the role of epigenetics in MM, with focus on the interplay between epigenetic mechanisms and the potential use of epigenetic inhibitors as future treatment modalities for MM.
引用
收藏
页码:101 / 115
页数:15
相关论文
共 251 条
[91]   CG13250, a novel bromodomain inhibitor, suppresses proliferation of multiple myeloma cells in an orthotopic mouse model [J].
Imayoshi, Natsuki ;
Yoshioka, Makoto ;
Chauhan, Jay ;
Nakata, Susumu ;
Toda, Yuki ;
Fletcher, Steven ;
Strovel, Jeffrey W. ;
Takata, Kazuyuki ;
Ashihara, Eishi .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 484 (02) :262-268
[92]   MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review [J].
Iorio, Marilena V. ;
Croce, Carlo M. .
EMBO MOLECULAR MEDICINE, 2012, 4 (03) :143-159
[93]   Functions of DNA methylation: islands, start sites, gene bodies and beyond [J].
Jones, Peter A. .
NATURE REVIEWS GENETICS, 2012, 13 (07) :484-492
[94]   Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma [J].
Kaiser, Martin F. ;
Johnson, David C. ;
Wu, Ping ;
Walker, Brian A. ;
Brioli, Annamaria ;
Mirabella, Fabio ;
Wardell, Christopher P. ;
Melchor, Lorenzo ;
Davies, Faith E. ;
Morgan, Gareth J. .
BLOOD, 2013, 122 (02) :219-226
[95]   Polycomb Target Genes Are Silenced in Multiple Myeloma [J].
Kalushkova, Antonia ;
Fryknas, Marten ;
Lemaire, Miguel ;
Fristedt, Charlotte ;
Agarwal, Prasoon ;
Eriksson, Maria ;
Deleu, Sarah ;
Atadja, Peter ;
Osterborg, Anders ;
Nilsson, Kenneth ;
Vanderkerken, Karin ;
Oberg, Fredrik ;
Jernberg-Wiklund, Helena .
PLOS ONE, 2010, 5 (07)
[96]   Decitabine improves patient outcomes in myelodysplastic syndromes - Resuits of a Phase III randomized study [J].
Kantarjian, H ;
Issa, JPJ ;
Rosenfeld, CS ;
Bennett, JM ;
Albitar, M ;
DiPersio, J ;
Klimek, V ;
Slack, J ;
de Castro, C ;
Ravandi, F ;
Helmer, R ;
Shen, LL ;
Nimer, SD ;
Leavitt, R ;
Raza, A ;
Saba, H .
CANCER, 2006, 106 (08) :1794-1803
[97]   RNA maps reveal new RNA classes and a possible function for pervasive transcription [J].
Kapranov, Philipp ;
Cheng, Jill ;
Dike, Sujit ;
Nix, David A. ;
Duttagupta, Radharani ;
Willingham, Aarron T. ;
Stadler, Peter F. ;
Hertel, Jana ;
Hackermueller, Joerg ;
Hofacker, Ivo L. ;
Bell, Ian ;
Cheung, Evelyn ;
Drenkow, Jorg ;
Dumais, Erica ;
Patel, Sandeep ;
Helt, Gregg ;
Ganesh, Madhavan ;
Ghosh, Srinka ;
Piccolboni, Antonio ;
Sementchenko, Victor ;
Tammana, Hari ;
Gingeras, Thomas R. .
SCIENCE, 2007, 316 (5830) :1484-1488
[98]   Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients [J].
Keats, JJ ;
Maxwell, CA ;
Taylor, BJ ;
Hendzel, MJ ;
Chesi, M ;
Bergsagel, PL ;
Larratt, LM ;
Mant, MJ ;
Reiman, T ;
Belch, AR ;
Pilarski, LM .
BLOOD, 2005, 105 (10) :4060-4069
[99]   In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression [J].
Keats, JJ ;
Reiman, T ;
Maxwell, CA ;
Taylor, BJ ;
Larratt, LM ;
Mant, MJ ;
Belch, AR ;
Pilarski, LM .
BLOOD, 2003, 101 (04) :1520-1529
[100]   Clonal competition with alternating dominance in multiple myeloma [J].
Keats, Jonathan J. ;
Chesi, Marta ;
Egan, Jan B. ;
Garbitt, Victoria M. ;
Palmer, Stephen E. ;
Braggio, Esteban ;
Van Wier, Scott ;
Blackburn, Patrick R. ;
Baker, Angela S. ;
Dispenzieri, Angela ;
Kumar, Shaji ;
Rajkumar, S. Vincent ;
Carpten, John D. ;
Barrett, Michael ;
Fonseca, Rafael ;
Stewart, A. Keith ;
Bergsagel, P. Leif .
BLOOD, 2012, 120 (05) :1067-1076