Chapter 1 – Pathophysiology

Contributors: Hervé Avet-Loiseau and Jill Corre


1 Laï JL, Zandecki M, Mary JY, et al. Improved cytogenetics in multiple myeloma: a study of 151 patients including 117 patients at diagnosis. Blood. 1995;85:2490-2497.
2 Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C, Groupe Français de Cytogénétique Hématologique. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98:2229-2238.
3 Bergsagel PL, Chesi M, Nardini E, Brents LA, Kirby SL, Kuehl WM. Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma. Proc Natl Acad Sci USA. 1996;93:13931-13936.

4 Chesi M, Bergsagel PL, Brents LA, Smith CM, Gerhard DS, Kuehl WM. Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines. Blood. 1996;88:674-681.
5 Chesi M, Nardini E, Lim RSC, et al. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 1998;92:3025-3034.
6 Chesi M, Bergsagel PL, Shonukan OO, et al. Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood. 1998;91:4457-4463.
7 Magrangeas F, Avet-Loiseau H, Gouraud W, et al. Minor clone provides a reservoir for relapse in multiple myeloma. Leukemia. 2013;27:473-481.
8 Keats JJ, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012;120:1067-1076.
9 Walker BA, Wardell CP, Melchor L, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia. 2014;28:384-390.
10 Egan JB, Shi CX, Tembe W, et al. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012;120:1060-1066.
11 Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471:467-472.
12 Bolli N, Avet-Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997-3003.
13 Lohr JG, Stojanov P, Carter SL, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25:91-101.
14 Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109:3489-3495.
15 Hebraud B, Leleu X, Lauwers-Cances V, et al. Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia. 2014;28:675-679.
16 Avet-Loiseau H, Malard F, Campion L, et al. Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor? Blood. 2011;117:2009-2011.
17 Zhan F, Hardin J, Kordsmeier B, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood. 2002;99:1745-1757.
18 Zhan F, Huang Y, Colla S, et al. The molecular classification of multiple myeloma. Blood. 2006;108:2020-2028.
19 Broyl A, Hose D, Lokhorst H, et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood. 2010;116:2543-2553.
20 Bianco P, Sacchetti B, Riminucci M. Osteoprogenitors and the hematopoietic microenvironment. Best Pract Res Clin Haematol. 2011;24:37-47.
21 Nagasawa T. Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol. 2006;6:107-116.
22 Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007;7:585-598.
23 Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia. 2009;23:10-24.
24 Manier S, Sacco A, Leleu X, Ghobrial IM, Roccaro AM. Bone marrow microenvironment in multiple myeloma progression. J Biomed Biotechnol. 2012;2012:157496.
25 Klein B, Tarte K, Jourdan M, et al. Survival and proliferation factors of normal and malignant plasma cells. Int J Hematol. 2003;78:106-113.
26 De Vos J, Hose D, Rème T, et al. Microarray-based understanding of normal and malignant plasma cells. Immunol Rev. 2006;210:86-104.
27 Sprynski AC, Hose D, Caillot L, et al. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor. Blood. 2009;113:4614-4626.
28 Klein B, Zhang XG, Lu ZY, Bataille R. Interleukin-6 in human multiple myeloma. Blood. 1995;85:863-872.
29 Gupta D, Treon SP, Shima Y, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia. 2001;15:1950-1961.
30 Ribatti D, Nico B, Vacca A. Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma. Oncogene. 2006;25:4257-4266.
31 Giuliani N, Storti P, Bolzoni M, Palma BD, Bonomini S. Angiogenesis and multiple myeloma. Cancer Microenviron. 2011;4:325-337.
32 Roodman GD. Pathogenesis of myeloma bone disease. J Cell Biochem. 2010;109:283-291.
33 Reagan MR, Ghobrial IM. Multiple myeloma mesenchymal stem cells: characterization, origin, and tumor-promoting effects. Clin Cancer Res. 2012;18:342-349.
34 Corre J, Mahtouk K, Attal M, et al. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. Leukemia. 2007;21:1079-1088.
35 Roccaro AM, Sacco A, Maiso P, et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest. 2013;123:1542-1555.
36 Mahtouk K, Hose D, Raynaud P, et al. Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma. Blood. 2007;109:4914-4923.
37 Corre J, Labat E, Espagnolle N, et al. Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Res. 2012;72:1395-1406.
38 Tarkun P, Birtas Atesoglu E, Mehtap O, Musul MM, Hacihanefioglu A. Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. Acta Haematol. 2014;131:173-178.
39 Raaijmakers MHGP, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852-857.