title: Implications of heterogeneity in multiple myeloma.
abstract: Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore.
authors.forename: Sanjay
authors.initials: S
authors.lastname: de Mel
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore.
authors.forename: Su Hong
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore.
authors.forename: Moon Ley
authors.initials: ML
authors.lastname: Tung
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute of Singapore, Singapore ; Cancer Science Institute of Singapore, National University of Singapore, Singapore ; National University Health System, NUHS Tower Block, Level 7, 1E Lower Kent Ridge Road, Singapore 119228.
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002869:Chromosome Aberrations; D018740:Genetic Heterogeneity; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
references.citation: Leukemia. 2008 Dec;22(12):2280-4
references.pmid: 18528420
references.citation: Blood. 2008 Feb 1;111(3):1603-9
references.pmid: 18006703
references.citation: Genes Chromosomes Cancer. 2011 Oct;50(10):765-74
references.pmid: 21961181
references.citation: Leukemia. 2007 Mar;21(3):582-4
references.pmid: 17215851
references.citation: Genomics. 1994 Sep 15;23(2):457-63
references.pmid: 7835896
references.citation: J Clin Oncol. 2013 Jul 10;31(20):2540-7
references.pmid: 23733781
references.citation: Leukemia. 2011 Jun;25(6):1026-35
references.pmid: 21468039
references.citation: Blood. 2011 Jul 21;118(3):675-8
references.pmid: 21628407
references.citation: Leukemia. 2010 Apr;24(4):833-42
references.pmid: 20220778
references.citation: J Clin Oncol. 2005 May 20;23(15):3412-20
references.pmid: 15809451
references.citation: Nat Rev Genet. 2012 Nov;13(11):795-806
references.pmid: 23044827
references.citation: Haematologica. 2012 Jul;97(7):1020-8
references.pmid: 22271890
references.citation: Blood. 2003 Oct 1;102(7):2562-7
references.pmid: 12805059
references.citation: Cancer Cell. 2007 Aug;12(2):131-44
references.pmid: 17692805
references.citation: Blood. 2009 May 28;113(22):5412-7
references.pmid: 19179464
references.citation: Leukemia. 2014 Mar;28(3):675-9
references.pmid: 23892719
references.citation: Blood. 2005 Jan 1;105(1):317-23
references.pmid: 15339850
references.citation: Blood. 1998 Mar 15;91(6):1873-81
references.pmid: 9490669
references.citation: Leukemia. 2012 Nov;26(11):2406-13
references.pmid: 22722715
references.citation: Blood. 2005 Sep 15;106(6):2156-61
references.pmid: 15920009
references.citation: J Clin Oncol. 2012 Jun 1;30(16):1949-52
references.pmid: 22547600
references.citation: Best Pract Res Clin Haematol. 2007 Dec;20(4):625-35
references.pmid: 18070710
references.citation: Blood. 2008 Mar 15;111(6):2962-72
references.pmid: 18332230
references.citation: Leukemia. 2012 Feb;26(2):349-55
references.pmid: 21836613
references.citation: Cancer Res. 2008 Jan 1;68(1):190-7
references.pmid: 18172311
references.citation: Blood. 2014 Jan 30;123(5):632-9
references.pmid: 24335104
references.citation: Blood. 2012 Aug 2;120(5):1060-6
references.pmid: 22529291
references.citation: Cancer Cell. 2013 Sep 9;24(3):289-304
references.pmid: 24029229
references.citation: J Clin Oncol. 2010 Mar 20;28(9):1599-605
references.pmid: 20177027
references.citation: Blood. 2009 May 28;113(22):5418-22
references.pmid: 19234139
references.citation: Blood. 2007 Apr 15;109(8):3489-95
references.pmid: 17209057
references.citation: Acta Oncol. 2000;39(7):765-70
references.pmid: 11145430
references.citation: Leukemia. 2014 Feb;28(2):269-77
references.pmid: 23974982
references.citation: Am J Pathol. 2004 Jul;165(1):71-81
references.pmid: 15215163
references.citation: Blood. 2001 Nov 15;98(10):3082-6
references.pmid: 11698294
references.citation: Blood. 1996 Dec 15;88(12):4711-8
references.pmid: 8977265
references.citation: Blood. 1981 Feb;57(2):333-8
references.pmid: 7448427
references.citation: Haematologica. 2011 Apr;96(4):574-82
references.pmid: 21173094
references.citation: Hematol Oncol Clin North Am. 1997 Feb;11(1):43-9
references.pmid: 9081203
references.citation: Nat Rev Cancer. 2002 Jan;2(1):48-58
references.pmid: 11902585
references.citation: Blood. 2004 Mar 15;103(6):2332-6
references.pmid: 14630803
references.citation: Cancer Cell. 2008 Feb;13(2):167-80
references.pmid: 18242516
references.citation: Blood Cells Mol Dis. 2012 Apr 15;48(4):247-53
references.pmid: 22341562
references.citation: Blood. 2013 Aug 22;122(8):1437-47
references.pmid: 23847194
references.citation: Leukemia. 2013 Mar;27(3):711-7
references.pmid: 23032723
references.citation: Blood. 2008 Nov 15;112(10):4017-23
references.pmid: 18669875
references.citation: Haematologica. 2010 Nov;95(11):1973-6
references.pmid: 20634494
references.citation: Blood. 2009 Jun 25;113(26):6669-80
references.pmid: 19401561
references.citation: Blood. 2000 Apr 15;95(8):2666-71
references.pmid: 10753849
references.citation: Clin Cancer Res. 2012 Nov 15;18(22):6155-68
references.pmid: 22988056
references.citation: Blood. 2013 Jan 10;121(2):318-28
references.pmid: 23169779
references.citation: Clin Cancer Res. 2011 Dec 15;17(24):7776-84
references.pmid: 21994415
references.citation: J Clin Invest. 1977 Oct;60(4):846-54
references.pmid: 302265
references.citation: Cancer Cell. 2014 Jan 13;25(1):91-101
references.pmid: 24434212
references.citation: Blood. 2011 May 5;117(18):4696-700
references.pmid: 21292777
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: Cancer. 1975 Sep;36(3):842-54
references.pmid: 1182674
references.citation: Nature. 2011 Mar 24;471(7339):467-72
references.pmid: 21430775
references.citation: Best Pract Res Clin Haematol. 2007 Dec;20(4):571-96
references.pmid: 18070707
references.citation: Br J Haematol. 1994 May;87(1):68-74
references.pmid: 7947257
references.citation: Blood. 2005 Jul 1;106(1):296-303
references.pmid: 15755896
references.citation: Leukemia. 2014 Feb;28(2):384-390
references.pmid: 23817176
references.citation: Cancer Discov. 2013 Aug;3(8):862-9
references.pmid: 23612012
references.citation: Leukemia. 2014 Aug;28(8):1725-1735
references.pmid: 24518206
references.citation: Nature. 2011 Feb 24;470(7335):476-7
references.pmid: 21350479
references.citation: Blood. 2003 Jun 1;101(11):4569-75
references.pmid: 12576322
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4048-53
references.pmid: 17360475
references.citation: Oncotarget. 2013 Aug;4(8):1230-40
references.pmid: 23985559
references.citation: PLoS One. 2013 Jun 20;8(6):e66361
references.pmid: 23840451
references.citation: PLoS One. 2010 Sep 01;5(9):
references.pmid: 20824134
references.citation: Haematologica. 2005 Oct;90(10):1365-72
references.pmid: 16219573
references.citation: Cancer Res. 2004 Feb 15;64(4):1546-58
references.pmid: 14989251
references.citation: Leukemia. 2006 Nov;20(11):2034-40
references.pmid: 17024118
references.citation: Nat Rev Cancer. 2012 Apr 12;12(5):335-48
references.pmid: 22495321
references.citation: Clin Cancer Res. 2010 Mar 15;16(6):1856-64
references.pmid: 20215539
references.citation: Blood. 2006 Sep 1;108(5):1724-32
references.pmid: 16705089
references.citation: Biol Blood Marrow Transplant. 2006 Jan;12(1 Suppl 1):77-80
references.pmid: 16399589
references.citation: Cancer Cell. 2007 Aug;12(2):115-30
references.pmid: 17692804
references.citation: Leukemia. 2009 Dec;23(12):2210-21
references.pmid: 19798094
references.citation: Clin Cancer Res. 2002 Oct;8(10):3198-204
references.pmid: 12374689
references.citation: Exp Hematol. 2009 Feb;37(2):234-44
references.pmid: 19135901
references.citation: Blood. 2011 Feb 10;117(6):2009-11
references.pmid: 20962323
references.citation: PLoS One. 2012;7(7):e42161
references.pmid: 22860071
references.citation: Leukemia. 2014 Mar;28(3):525-42
references.pmid: 24253022
references.citation: J Clin Oncol. 2008 Oct 10;26(29):4798-805
references.pmid: 18591550
references.citation: Haematologica. 2011 Jan;96(1):87-95
references.pmid: 20884712
references.citation: Blood. 2011 Dec 1;118(23):5989-95
references.pmid: 21900189