title: MMSET: role and therapeutic opportunities in multiple myeloma.
abstract: Recurrent chromosomal translocations are central to the pathogenesis, diagnosis, and prognosis of hematologic malignancies. The translocation t(4; 14)(p16; q32) is one of the most common translocations in multiple myeloma (MM) and is associated with very poor prognosis. The t(4; 14) translocation leads to the simultaneous overexpression of two genes, FGFR3 (fibroblast growth factor receptor 3) and MMSET (multiple myeloma SET domain), both of which have potential oncogenic activity. However, approximately 30% of t(4; 14) MM patients do not express FGFR3 and have poor prognosis irrespective of FGFR3 expression, whereas MMSET overexpression is universal in t(4; 14) cases. In this review, we provide an overview of recent findings regarding the oncogenic roles of MMSET in MM and its functions on histone methylation. We also highlight some of MMSET partners and its downstream signalling pathways and discuss the potential therapeutics targeting MMSET.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599.
authors.forename: Zhigang
authors.identifier: 0000-0002-6600-8190
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599 ; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228 ; Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore 119228.
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D051498:Receptor, Fibroblast Growth Factor, Type 3
references.citation: J Clin Oncol. 2005 Sep 10;23(26):6333-8
references.pmid: 16155016
references.citation: Cell Mol Life Sci. 2007 Oct;64(19-20):2590-606
references.pmid: 17599239
references.citation: Blood. 2003 Mar 15;101(6):2374-6
references.pmid: 12433679
references.citation: Nature. 2011 Feb 3;470(7332):124-8
references.pmid: 21293379
references.citation: Nat Rev Clin Oncol. 2011 Apr 26;8(8):479-91
references.pmid: 21522124
references.citation: Nat Med. 2011 Mar;17(3):330-9
references.pmid: 21386836
references.citation: Haematologica. 2009 Jan;94(1):78-86
references.pmid: 19059936
references.citation: Mol Cell. 2011 Nov 18;44(4):609-20
references.pmid: 22099308
references.citation: Mol Cell Biol. 2012 Aug;32(15):3121-31
references.pmid: 22645312
references.citation: Semin Oncol. 2013 Oct;40(5):618-33
references.pmid: 24135407
references.citation: Epigenetics. 2013 May;8(5):457-63
references.pmid: 23625014
references.citation: Br J Haematol. 2005 Oct;131(2):214-8
references.pmid: 16197452
references.citation: Blood. 2008 Mar 15;111(6):3145-54
references.pmid: 18156491
references.citation: Cell. 2012 Jul 6;150(1):12-27
references.pmid: 22770212
references.citation: Nature. 2009 Jul 9;460(7252):287-91
references.pmid: 19483677
references.citation: EMBO J. 1998 Jun 15;17(12):3398-412
references.pmid: 9628876
references.citation: Oncogene. 2013 Jun 6;32(23):2882-90
references.pmid: 22797064
references.citation: Mol Cell Biol. 2008 Mar;28(6):2023-34
references.pmid: 18172012
references.citation: PLoS One. 2011;6(6):e18919
references.pmid: 21720545
references.citation: Immunol Rev. 2003 Aug;194:96-104
references.pmid: 12846810
references.citation: J Biol Chem. 2005 Oct 21;280(42):35261-71
references.pmid: 16118227
references.citation: Biochim Biophys Acta. 2011 Dec;1816(2):158-63
references.pmid: 21664949
references.citation: Mol Cell. 2014 Jan 23;53(2):247-61
references.pmid: 24389101
references.citation: Leukemia. 2013 Mar;27(3):686-94
references.pmid: 22972034
references.citation: Neoplasia. 2011 Oct;13(10):887-98
references.pmid: 22028615
references.citation: Hum Mol Genet. 1998 Jul;7(7):1071-82
references.pmid: 9618163
references.citation: J Biol Chem. 2009 Dec 4;284(49):34283-95
references.pmid: 19808676
references.citation: Genomics. 2001 May 15;74(1):79-88
references.pmid: 11374904
references.citation: Nature. 2006 Jul 6;442(7098):100-3
references.pmid: 16728977
references.citation: Am J Respir Cell Mol Biol. 2001 Jan;24(1):90-98
references.pmid: 11152655
references.citation: Blood. 1998 Nov 1;92(9):3025-34
references.pmid: 9787135
references.citation: Oncotarget. 2013 Jul;4(7):1008-18
references.pmid: 23900284
references.citation: Nat Rev Genet. 2007 Mar;8(3):173-84
references.pmid: 17304245
references.citation: Biochem Biophys Res Commun. 2009 Feb 20;379(4):840-5
references.pmid: 19121287
references.citation: Cancer Res. 2013 Oct 15;73(20):6277-88
references.pmid: 23980095
references.citation: Blood. 2011 Jan 6;117(1):211-20
references.pmid: 20974671
references.citation: Blood. 2008 Jan 15;111(2):856-64
references.pmid: 17942756
references.citation: Blood. 2003 Feb 15;101(4):1520-9
references.pmid: 12393535
references.citation: Cancer Res. 2008 Mar 1;68(5):1247-50
references.pmid: 18316585
references.citation: Br J Haematol. 2010 Mar;148(5):702-13
references.pmid: 19912222
references.citation: FEBS Lett. 2009 Jun 18;583(12):1880-6
references.pmid: 19481544
references.citation: Blood. 2005 May 15;105(10):4060-9
references.pmid: 15677557
references.citation: Leuk Lymphoma. 2006 Nov;47(11):2289-300
references.pmid: 17107900