Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
International Journal of Hematology
Published in: International Journal of Hematology 3/2013

01-03-2013 | Progress in Hematology

Molecular pathogenesis of multiple myeloma: basic and clinical updates

Authors: Marta Chesi, P. Leif Bergsagel

Published in: International Journal of Hematology | Issue 3/2013

Login to get access

Abstract

Multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21, and lacks recurrent immunoglobulin gene translocations. Non-hyperdiploid myeloma in contrast is characterized by chromosome translocations t(4;14), t(14;16), t(14;20), t(6;14) and t(11;14). A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin D gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression of a MAF family transcription factor, or indirectly by as yet unidentified mechanisms. Secondary genetic events include rearrangements of MYC, activating mutations of NRAS, KRAS or BRAF, a promiscuous array of mutations that activate NFkB and deletions of 17p. Among the poor-risk genetic features are t(4;14), t(14;16), t(14;20), del 17p and gains of 1q. Available evidence supports the use of a risk-stratified approach to the treatment of patients with multiple myeloma, with the early and prolonged use of bortezomib particularly in patients with t(4;14) and del 17p.
Literature
1.
Malpas JS, Bergsagel DE, Kyle R, Anderson K. Multiple myeloma: biology and management. Oxford: Oxford University Press; 2004.
2.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER cancer statistics review 1975–2009 (Vintage 2009 Populations). Bethesda: National Cancer Institute; 2012. http://​seer.​cancer.​gov/​csr/​1975_​2009_​pops09/​.
3.
4.
Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, et al. Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol. 2012;30(16):1949–52.PubMedCrossRef
5.
Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002;2(3):175–87.PubMedCrossRef
6.
Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412–7.PubMedCrossRef
7.
Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418–22.PubMedCrossRef
8.
Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ, Colby CL, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721–8.PubMedCrossRef
9.
Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362–9.PubMedCrossRef
10.
Drexler HG, Matsuo Y. Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia. Leuk Res. 2000;24(8):681–703.PubMedCrossRef
11.
Gabrea A, Martelli ML, Qi Y, Roschke A, Barlogie B, Shaughnessy JD Jr, et al. Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors. Genes Chromosom Cancer. 2008;47(7):573–90.PubMedCrossRef
12.
Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene. 2001;20(40):5611–22.PubMedCrossRef
13.
Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International myeloma working group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210–21.PubMedCrossRef
14.
Avet-Loiseau H, Facon T, Daviet A, Godon C, Rapp MJ, Harousseau JL, et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res. 1999;59(18):4546–50.PubMed
15.
Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106(1):296–303.PubMedCrossRef
16.
Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, et al. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell. 2004;5(2):191–9.PubMedCrossRef
17.
Zingone A, Cultraro CM, Shin D-M, Bean CM, Morse HC, Janz S, et al. Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms. Leukemia. 2010;24(6):1171–8.PubMedCrossRef
18.
Qing J, Du X, Chen Y, Chan P, Li H, Wu P, et al. Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice. J Clin Invest. 2009;119(5):1216–29.PubMedCrossRef
19.
Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, et al. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005;105(7):2941–8.PubMedCrossRef
20.
Marango J, Shimoyama M, Nishio H, Meyer JA, Min D-J, Sirulnik A, et al. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood. 2008;111(6):3145–54.PubMedCrossRef
21.
Martinez-Garcia E, Popovic R, Min D-J, Sweet SMM, Thomas PM, Zamdborg L, et al. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood. 2011;117(1):211–20.PubMedCrossRef
22.
Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, et al. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol Cell. 2011;44(4):609–20.PubMedCrossRef
23.
Pei H, Zhang L, Luo K, Qin Y, Chesi M, Fei F, et al. MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. Nature. 2011;470(7332):124–8.PubMedCrossRef
24.
Min DJ, Ezponda T, Kim MK, Will CM, Martinez-Garcia E, Popovic R, et al. MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC. Leukemia. 2012. doi:10.​1038/​leu.​2012.​269.
25.
Asangani IA, Ateeq B, Cao Q, Dodson L, Pandhi M, Kunju LP, et al. Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer. Mol Cell. 2013;49(1):80–93.PubMed
26.
Hudlebusch HR, Santoni-Rugiu E, Simon R, Ralfkiaer E, Rossing HH, Johansen JV, et al. The histone methyltransferase and putative oncoprotein MMSET is overexpressed in a large variety of human tumors. Clin Cancer Res. 2011;17(9):2919–33.PubMedCrossRef
27.
Ezponda T, Popovic R, Shah MY, Martinez-Garcia E, Zheng Y, Min DJ, et al. The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial-mesenchymal transition and invasive properties of prostate cancer. Oncogene. 2012.
28.
Yang P, Guo L, Duan ZJ, Tepper CG, Xue L, Chen X, et al. Histone methyltransferase NSD2/MMSET mediates constitutive NF-kappaB signaling for cancer cell proliferation, survival, and tumor growth via a feed-forward loop. Mol Cell Biol. 2012;32(15):3121–31.PubMedCrossRef
29.
Fonseca R, Debes-Marun CS, Picken EB, Dewald GW, Bryant SC, Winkler JM, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003;102(7):2562–7.PubMedCrossRef
30.
Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA, et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood. 2012;119(9):2100–5.PubMedCrossRef
31.
Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S, et al. The molecular classification of multiple myeloma. Blood. 2006;108(6):2020–8.PubMedCrossRef
32.
Broyl A, Hose D, Lokhorst H, de Knegt Y, Peeters J, Jauch A, et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood. 2010;116(14):2543–53.PubMedCrossRef
33.
Nair B, van Rhee F, Shaughnessy JD, Anaissie E, Szymonifka J, Hoering A, et al. Superior results of total therapy 3 (2003–33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006–66 with VRD maintenance. Blood. 2010;115(21):4168–73.PubMedCrossRef
34.
Chng WJ, Huang GF, Chung T-H, Ng SB, Gonzalez-Paz N, Troska-Price T, et al. Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma. Leukemia. 2011;25(6):1026–35.PubMedCrossRef
35.
Chesi M, Robbiani DF, Sebag M, Chng WJ, Affer M, Tiedemann R, et al. AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies. Cancer Cell. 2008;13(2):167–80.PubMedCrossRef
36.
Chesi M, Matthews GM, Garbitt VM, Palmer SE, Shortt J, Lefebure M, et al. Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy. Blood. 2012;120(2):376–85.PubMedCrossRef
37.
Dib A, Gabrea A, Glebov OK, Bergsagel PL, Kuehl WM. Characterization of MYC translocations in multiple myeloma cell lines. J Natl Cancer Inst. 2008;39:25–31.
38.
Avet-Loiseau H, Gerson F, Magrangeas F, Minvielle S, Harousseau JL, Bataille R. Rearrangements of the c-myc oncogene are present in 15 % of primary human multiple myeloma tumors. Blood. 2001;98(10):3082–6.PubMedCrossRef
39.
Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–17.PubMedCrossRef
40.
Chiecchio L, Dagrada GP, Ibrahim AH, Dachs Cabanas E, Protheroe RK, Stockley DM, et al. Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context. Haematologica. 2009;94(12):1708–13.PubMedCrossRef
41.
Walker BA, Wardell CP, Melchor L, Hulkki S, Potter NE, Johnson DC, et al. Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma. Blood. 2012;120(5):1077–86.PubMedCrossRef
42.
Chng WJ, Gonzalez-Paz N, Price-Troska T, Jacobus S, Rajkumar SV, Oken MM, et al. Clinical and biological significance of RAS mutations in multiple myeloma. Leukemia. 2008;22(12):2280–4.PubMedCrossRef
43.
Zingone A, Kuehl WM. Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myeloma. Semin Hematol. 2011;48(1):4–12.PubMedCrossRef
44.
Haigis KM, Kendall KR, Wang Y, Cheung A, Haigis MC, Glickman JN, et al. Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon. Nat Genet. 2008;40(5):600–8.PubMedCrossRef
45.
Rasmussen T, Haaber J, Dahl IM, Knudsen LM, Kerndrup GB, Lodahl M, et al. Identification of translocation products but not K-RAS mutations in memory B cells from patients with multiple myeloma. Haematologica. 2010;95(10):1730–7.PubMedCrossRef
46.
Rasmussen T, Kuehl M, Lodahl M, Johnsen HE, Dahl IMS. Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors. Blood. 2005;105(1):317–23.PubMedCrossRef
47.
Steinbrunn T, Stühmer T, Gattenlöhner S, Rosenwald A, Mottok A, Unzicker C, et al. Mutated RAS and constitutively activated Akt delineate distinct oncogenic pathways, which independently contribute to multiple myeloma cell survival. Blood. 2011;117(6):1998–2004.PubMedCrossRef
48.
Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467–72.PubMedCrossRef
49.
Elgueta R, de Vries VC, Noelle RJ. The immortality of humoral immunity. Immunol Rev. 2011;236:139–50.CrossRef
50.
Annunziata CM, Davis RE, Demchenko Y, Bellamy W, Gabrea A, Zhan F, et al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell. 2007;12(2):115–30.PubMedCrossRef
51.
Keats JJ, Fonseca R, Chesi M, Schop R, Baker A, Chng WJ, et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007;12(2):131–44.PubMedCrossRef
52.
Demchenko YN, Glebov OK, Zingone A, Keats JJ, Bergsagel PL, Kuehl WM. Classical and/or alternative NF-kappaB pathway activation in multiple myeloma. Blood. 2010;115(17):3541–52.PubMedCrossRef
53.
Rossi JF, Moreaux J, Hose D, Requirand G, Rose M, Rouillé V, et al. Atacicept in relapsed/refractory multiple myeloma or active Waldenström’s macroglobulinemia: a phase I study. Br J Cancer. 2009;101(7):1051–8.PubMedCrossRef
54.
Tiedemann RE, Gonzalez-Paz N, Kyle RA, Santana-Davila R, Price-Troska T, Van Wier SA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia. 2008;22(5):1044–52.PubMedCrossRef
55.
Lode L, Eveillard M, Trichet V, Soussi T, Wuilleme S, Richebourg S, et al. Mutations in TP53 are exclusively associated with del(17p) in multiple myeloma. Haematologica. 2010;95(11):1973–6.PubMedCrossRef
56.
Pichiorri F, Suh S–S, Rocci A, De Luca L, Taccioli C, Santhanam R, et al. Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell. 2010;18(4):367–81.PubMedCrossRef
57.
Walker BA, Leone PE, Chiecchio L, Dickens NJ, Jenner MW, Boyd KD, et al. A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood. 2010;116(15):e56–65.PubMedCrossRef
58.
Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, et al. Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res. 2011;17(24):7776–84.PubMedCrossRef
59.
Dib A, Peterson TR, Raducha-Grace L, Zingone A, Zhan F, Hanamura I, et al. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression. Cell Div. 2006;1:23.PubMedCrossRef
60.
Avet-Loiseau H, Li C, Magrangeas F, Gouraud W, Charbonnel C, Harousseau J-L, et al. Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol. 2009;27(27):4585–90.PubMedCrossRef
61.
Keats JJ, Chesi M, Egan JB, Garbitt VM, Palmer SE, Braggio E, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012;120(5):1067–76.PubMedCrossRef
62.
Walker BA, Wardell CP, Chiecchio L, Smith EM, Boyd KD, Neri A, et al. Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood. 2011;117(2):553–62.PubMedCrossRef
63.
Salhia B, Baker A, Ahmann G, Auclair D, Fonseca R, Carpten J. DNA methylation analysis determines the high frequency of genic hypomethylation and low frequency of hypermethylation events in plasma cell tumors. Cancer Res. 2010;70(17):6934–44.PubMedCrossRef
64.
Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, et al. MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA. 2008;105(35):12885–90.PubMedCrossRef
65.
Magrangeas F, Avet-Loiseau H, Gouraud W, Lode L, Decaux O, Godmer P, et al. Minor clone provides a reservoir for relapse in multiple myeloma. Leukemia. 2013;27:473–81.
66.
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109(8):3489–95.PubMedCrossRef
67.
Kapoor P, Kumar S, Fonseca R, Lacy MQ, Witzig TE, Hayman SR, et al. Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood. 2009;114(3):518–21.PubMedCrossRef
68.
Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28(30):4630–4.PubMedCrossRef
69.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946–55.PubMedCrossRef
70.
San-Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–17.PubMedCrossRef
71.
Pineda-Roman M, Zangari M, Haessler J, Anaissie E, Tricot G, van Rhee F, et al. Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol. 2008;140(6):625–34.PubMedCrossRef
72.
Barlogie B, Pineda-Roman M, van Rhee F, Haessler J, Anaissie E, Hollmig K, et al. Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008;112(8):3115–21.PubMedCrossRef
73.
Morgan GJ, Gregory WM, Davies FE, Bell SE, Szubert AJ, Brown JM, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood. 2012;119(1):7–15.PubMedCrossRef
74.
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108(10):3289–94.PubMedCrossRef
75.
Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011;118(5):1231–8.PubMedCrossRef
76.
Mateos M-V, Oriol A, Martínez-López J, Gutiérrez N, Teruel A-I, de Paz R, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010;11(10):934–41.PubMedCrossRef
77.
Neben K, Lokhorst HM, Jauch A, Bertsch U, Hielscher T, van der Holt B, et al. Administration of bortezomib before and after autologous stem-cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119(4):940–8.PubMedCrossRef
78.
Avet-Loiseau H, Caillot D, Marit G, Lauwers-Cances V, Roussel M, Facon T, et al. Long-term maintenance with lenalidomide improves progression free survival in myeloma patients with high-risk cytogenetics: An IFM study. ASH Annual Meeting Abstracts. 2010;116(21):1944.
79.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782–91.PubMedCrossRef
80.
Ross FM, Chiecchio L, Dagrada G, Protheroe RKM, Stockley DM, Harrison CJ, et al. The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance. Haematologica. 2010;95(7):1221–5.PubMedCrossRef
81.
Avet-Loiseau H, Malard F, Campion L, Magrangeas F, Sebban C, Lioure B, et al. Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor? Blood. 2011;117(6):2009–11.PubMedCrossRef
82.
Hose D, Reme T, Hielscher T, Moreaux J, Messner T, Seckinger A, et al. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma. Haematologica. 2011;96(1):87–95.PubMedCrossRef
83.
Shaughnessy JD, Zhan F Jr, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276–84.PubMedCrossRef
84.
Decaux O, Lode L, Magrangeas F, Charbonnel C, Gouraud W, Jézéquel P, et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2008;26(29):4798–805.PubMedCrossRef
85.
Kumar SK, Mikhael JR, Buadi FK, Dingli D, Dispenzieri A, Fonseca R, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84(12):1095–110.PubMedCrossRef
86.
Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro-Coy N, et al. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012;97(3):442–50.PubMedCrossRef
Metadata
Title
Molecular pathogenesis of multiple myeloma: basic and clinical updates
Authors
Marta Chesi
P. Leif Bergsagel
Publication date
01-03-2013
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-013-1291-2

Other articles of this Issue 3/2013

International Journal of Hematology 3/2013 Go to the issue

Original Article

Prognostic value of Waldeyer’s ring involvement of diffuse large B-cell lymphoma treated with R-CHOP

Original Article

Risk factors influencing mortality related to Stenotrophomonas maltophilia infection in hematology–oncology patients

Progress in Hematology

Current approaches for the treatment of multiple myeloma

Letter to the Editor

JAK2 V617F mutation positive primary myelofibrosis with concomitant t(9;11;22)(q34;p15;q11.2) but no BCR/ABL fusion

Original Article

JAK2 46/1 haplotype is associated with JAK2 V617F-positive myeloproliferative neoplasms in Japanese patients

Original Article

Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits