title: The Tao of myeloma.
abstract: Multiple myeloma is a plasma cell malignancy in which significant advances have been observed during the last 15 years. Our understanding of the disease has been advanced through its molecular characterization. We have also seen improvements in patient care with the development of 2 new classes of active agents, proteasome inhibitors and immunomodulatory drugs (IMiDs), resulting in a significant improvement in overall survival of myeloma patients such that it can now be debated as to whether some subsets of myeloma patients can be cured. However, the advances in our understanding of myeloma biology occurred in parallel with advances in treatment as opposed to being directly informed by the research. Moreover, the molecular characterization of malignant plasma cells would not have predicted the effectiveness of these novel therapies.We hypothesize that proteasome inhibitors and IMiDs are highly active because malignant plasma cells are constrained by many of the characteristics of their normal counterparts and these novel therapies target both normal plasma cell biology and the cancer biology of myeloma. Thus, a better understanding of normal plasma cell biology will likely yield as many actionable targets as mapping the genomic landscape of this disease.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Boise
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Lee
mesh_terms: D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D007155:Immunologic Factors / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000209:etiology* / Q000235:genetics / Q000628:therapy*; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology; D061988:Proteasome Inhibitors / Q000627:therapeutic use
chemical_list: D007147:Immunoglobulin Light Chains; D007155:Immunologic Factors; D061988:Proteasome Inhibitors
references.citation: Blood. 2011 May 12;117(19):5157-65
references.pmid: 21389327
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10967-71
references.pmid: 20534453
references.citation: Blood. 2010 May 20;115(20):4007-8
references.pmid: 20489059
references.citation: Br J Haematol. 2013 Jun;161(5):695-700
references.pmid: 23565715
references.citation: Blood. 2012 Jul 12;120(2):376-85
references.pmid: 22451422
references.citation: Cell. 2011 Sep 16;146(6):904-17
references.pmid: 21889194
references.citation: Clin Cancer Res. 1998 Jun;4(6):1521-6
references.pmid: 9626472
references.citation: N Engl J Med. 1996 Jul 11;335(2):91-7
references.pmid: 8649495
references.citation: Br J Haematol. 2011 Sep;154(6):745-54
references.pmid: 21777223
references.citation: Blood. 2012 Aug 2;120(5):1077-86
references.pmid: 22573403
references.citation: J Transplant. 2012;2012:201754
references.pmid: 22545199
references.citation: Haematologica. 2009 Feb;94(2):270-5
references.pmid: 19144659
references.citation: Cancer Cell. 2007 Aug;12(2):131-44
references.pmid: 17692805
references.citation: Int J Hematol. 2013 Mar;97(3):306-12
references.pmid: 23420183
references.citation: Blood. 2008 Mar 1;111(5):2516-20
references.pmid: 17975015
references.citation: Semin Oncol. 2013 Oct;40(5):652-8
references.pmid: 24135409
references.citation: Semin Immunol. 2011 Oct;23(5):341-9
references.pmid: 21924923
references.citation: Br J Haematol. 2011 Aug;154(3):325-36
references.pmid: 21707574
references.citation: Cancer Res. 2007 Dec 15;67(24):11914-23
references.pmid: 18089822
references.citation: PLoS One. 2013 Oct 29;8(10):e77608
references.pmid: 24204892
references.citation: Trends Immunol. 2011 Dec;32(12):595-602
references.pmid: 22001488
references.citation: Oncology (Williston Park). 2013 Sep;27(9):924-8, 930
references.pmid: 24282993
references.citation: J Clin Invest. 2012 Oct;122(10):3456-63
references.pmid: 23023717
references.citation: Blood. 2012 Aug 2;120(5):1060-6
references.pmid: 22529291
references.citation: Blood. 2010 Aug 5;116(5):679-86
references.pmid: 20385792
references.citation: Cancer Cell. 2013 Sep 9;24(3):289-304
references.pmid: 24029229
references.citation: Cell Metab. 2008 Jan;7(1):11-20
references.pmid: 18177721
references.citation: Blood. 2006 Nov 15;108(10):3441-9
references.pmid: 16728695
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8567-72
references.pmid: 15937109
references.citation: Leuk Res. 2014 Jan;38(1):23-8
references.pmid: 24129344
references.citation: Nature. 2008 Jul 10;454(7201):226-31
references.pmid: 18568025
references.citation: Trials. 2014 Apr 03;15:107
references.pmid: 24708575
references.citation: Transplantation. 2010 Feb 15;89(3):277-84
references.pmid: 20145517
references.citation: Nature. 2011 Feb 3;470(7332):124-8
references.pmid: 21293379
references.citation: Cancer Res. 2010 Jun 1;70(11):4318-26
references.pmid: 20460535
references.citation: J Allergy Clin Immunol. 2013 Apr;131(4):959-71
references.pmid: 23465663
references.citation: N Engl J Med. 2013 Jan 3;368(1):90-2
references.pmid: 23281998
references.citation: Cancer Res. 2009 Dec 15;69(24):9367-75
references.pmid: 19934314
references.citation: Science. 2014 Jan 17;343(6168):301-5
references.pmid: 24292625
references.citation: Cancer Cell. 2013 Apr 15;23(4):435-49
references.pmid: 23541952
references.citation: Blood. 2002 Mar 15;99(6):1885-93
references.pmid: 11877256
references.citation: Cancer Cell. 2008 Feb;13(2):167-80
references.pmid: 18242516
references.citation: Blood. 2000 Aug 15;96(4):1274-9
references.pmid: 10942368
references.citation: Blood. 2013 Jan 24;121(4):624-7
references.pmid: 23233657
references.citation: Blood. 2012 Jun 14;119(24):5772-81
references.pmid: 22538852
references.citation: Nat Med. 2008 Jul;14(7):748-55
references.pmid: 18542049
references.citation: Cancer Res. 2007 Aug 1;67(15):7395-405
references.pmid: 17671210
references.citation: Antioxid Redox Signal. 2014 Dec 10;21(17):2401-18
references.pmid: 24635140
references.citation: Expert Opin Biol Ther. 2013 Jun;13 Suppl 1:S69-82
references.pmid: 23782016
references.citation: J Exp Med. 2004 Jan 19;199(2):209-19
references.pmid: 14718515
references.citation: J Exp Med. 2011 Jul 4;208(7):1435-46
references.pmid: 21690252
references.citation: Blood. 2011 Nov 3;118(18):4771-9
references.pmid: 21860026
references.citation: Lancet Oncol. 2008 Dec;9(12):1157-65
references.pmid: 19038762
references.citation: Leuk Lymphoma. 2013 Feb;54(2):229-41
references.pmid: 22897729
references.citation: Blood. 2003 Jul 15;102(2):772-3
references.pmid: 12835230
references.citation: Blood. 2013 Jan 10;121(2):318-28
references.pmid: 23169779
references.citation: Semin Oncol. 2001 Dec;28(6):613-9
references.pmid: 11740819
references.citation: Blood. 2011 Dec 8;118(24):6368-79
references.pmid: 21917757
references.citation: Blood. 2006 Jun 15;107(12):4907-16
references.pmid: 16507771
references.citation: J Immunol. 2002 Oct 15;169(8):4213-21
references.pmid: 12370351
references.citation: Br J Haematol. 2008 May;141(4):413-22
references.pmid: 18318757
references.citation: Cancer Cell. 2014 Jan 13;25(1):91-101
references.pmid: 24434212
references.citation: Clin Cancer Res. 2013 Apr 15;19(8):2048-60
references.pmid: 23344265
references.citation: Blood. 2009 Jan 15;113(3):626-34
references.pmid: 18981296
references.citation: Nat Commun. 2014;5:2997
references.pmid: 24429703
references.citation: Blood. 2012 Aug 2;120(5):1067-76
references.pmid: 22498740
references.citation: Nature. 2011 Mar 24;471(7339):467-72
references.pmid: 21430775
references.citation: PLoS Comput Biol. 2012;8(3):e1002418
references.pmid: 22396639
references.citation: Leukemia. 2014 Feb;28(2):384-390
references.pmid: 23817176
references.citation: Kidney Int. 2012 Jun;81(11):1067-74
references.pmid: 22336990
references.citation: Leukemia. 2014 Aug;28(8):1725-1735
references.pmid: 24518206
references.citation: N Engl J Med. 1999 Nov 18;341(21):1565-71
references.pmid: 10564685
references.citation: Cancer Discov. 2013 Aug;3(8):862-9
references.pmid: 23612012
references.citation: Cancer Res. 2007 Feb 15;67(4):1783-92
references.pmid: 17308121
references.citation: Nat Chem Biol. 2010 Mar;6(3):238-243
references.pmid: 20139990
references.citation: Cell Mol Immunol. 2013 Mar;10(2):103-6
references.pmid: 23241902
references.citation: Blood Cancer J. 2014 Mar 14;4:e191
references.pmid: 24632883
references.citation: Nat Rev Cancer. 2012 Apr 12;12(5):335-48
references.pmid: 22495321
references.citation: Curr Opin Immunol. 2006 Jun;18(3):265-70
references.pmid: 16616478
references.citation: Blood. 2011 Aug 4;118(5):1329-39
references.pmid: 21659544
references.citation: Blood. 1994 Oct 15;84(8):2597-603
references.pmid: 7522634
references.citation: Am J Transplant. 2011 May;11(5):896-906
references.pmid: 21521465
references.citation: Blood. 2012 Mar 15;119(11):2579-89
references.pmid: 22262760
references.citation: Curr Opin Immunol. 2008 Apr;20(2):162-9
references.pmid: 18456483
references.citation: Science. 2014 Jan 17;343(6168):305-9
references.pmid: 24292623
references.citation: Blood. 2009 Mar 26;113(13):3040-9
references.pmid: 19164601
references.citation: Blood. 2010 Dec 9;116(24):5285-8
references.pmid: 20844234
references.citation: Transplantation. 2008 Dec 27;86(12):1754-61
references.pmid: 19104417
references.citation: CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
references.pmid: 24399786
references.citation: Blood. 2002 Jul 1;100(1):194-9
references.pmid: 12070027
references.citation: Science. 2010 Mar 12;327(5971):1345-50
references.pmid: 20223979
references.citation: Clin Lymphoma Myeloma Leuk. 2010 Jun;10(3):217-9
references.pmid: 20511168
references.citation: Blood. 2008 Oct 1;112(7):2917-26
references.pmid: 18641367
references.citation: Nat Immunol. 2013 Mar;14(3):290-7
references.pmid: 23377201
references.citation: Blood. 2011 Jan 27;117(4):1311-4
references.pmid: 21081713
references.citation: Blood. 2011 Jul 21;118(3):529-34
references.pmid: 21482708