Biopolym. Cell. 1997; 13(6):427-435.
Reviews
Molecular basis of multiple myeloma
1Telegeev G. D., 1Koliychuk A. N., 1Dybkov M. V., 1Maliuta S. S.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

The review summarizes the recent data on molecular biology, immunology and cytogenetics of multiple myeloma. Different views on the beginning stage of B cells tumor transformation is analyzed. The potential approach to further study of multiple myeloma is also disscussed.

References

[1] Niesvizky R, Siegel D, Michaeli J. Biology and treatment of multiple myeloma. Blood Rev. 1993;7(1):24-33.
[2] Riedel DA, Pottern LM. The epidemiology of multiple myeloma. Hematol Oncol Clin North Am. 1992;6(2):225-47.
[3] Kasyanenko IV, Pinchuk VG, Myasoyedov DV. et al. Oncology. handbook. Kiev: Naukova Dumka. 1992. 264 p.
[4] Davis DL, Hoel D, Fox J, Lopez A. International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and the USA. Lancet. 1990;336(8713):474-81.
[5] Shimizu Y, Kato H, Schull WJ. Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 2. Cancer mortality based on the recently revised doses (DS86). Radiat Res. 1990;121(2):120-41.
[6] Bhatia KG, Cherney BW, Huppi K, Magrath IT, Cossman J, Sausville E, Barriga F, Johnson B, Gause B, Bonney G, et al. A deletion linked to a poly(ADP-ribose) polymerase gene on chromosome 13q33-qter occurs frequently in the normal black population as well as in multiple tumor DNA. Cancer Res. 1990;50(17):5406-13.
[7] Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Fran?ais du My?lome. N Engl J Med. 1996;335(2):91-7.
[8] Demina EA, Votiakova OM. Alpha-interferon in present-day treatment of myeloma Gematol Transfuziol. 1996;41(2):32-6.
[9] Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol. 1992;10(2):334-42.
[10] Li YS, Hayakawa K, Hardy RR. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J Exp Med. 1993;178(3):951-60.
[11] Samo?lova RS. The ontogeny of normal human B-lymphocytes. Gematol Transfuziol. 1993;38(4):18-22.
[12] Alt FW, Blackwell TK, Yancopoulos GD. Development of the primary antibody repertoire. Science. 1987;238(4830):1079-87.
[13] Takemori T, Rajewsky K. Lambda chain expression at different stages of ontogeny in C57BL/6, BALB/c and SJL mice. Eur J Immunol. 1981;11(8):618-25.
[14] Tonegawa S. Somatic generation of antibody diversity. Nature. 1983;302(5909):575-81.
[15] Ehlich A, Schaal S, Gu H, Kitamura D, M?ller W, Rajewsky K. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell. 1993;72(5):695-704.
[16] Weissman IL. Developmental switches in the immune system. Cell. 1994;76(2):207-18.
[17] Hu MC, Siegelman MH, Holzmann B, Crowe DT, Weissman IL. Lymphocyte homing receptors. Cold Spring Harb Symp Quant Biol. 1992;57:291-308.
[18] Cline MJ. The molecular basis of leukemia. N Engl J Med. 1994;330(5):328-36.
[19] Jacob J, Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med. 1992;176(3):679-87.
[20] Clark EA, Ledbetter JA. How B and T cells talk to each other. Nature. 1994;367(6462):425-8.
[21] Miller C, Stedra J, Kelsoe G, Cerny J. Facultative role of germinal centers and T cells in the somatic diversification of IgVH genes. J Exp Med. 1995;181(4):1319-31.
[22] Gray D, Dullforce P, Jainandunsing S. Memory B cell development but not germinal center formation is impaired by in vivo blockade of CD40-CD40 ligand interaction. J Exp Med. 1994;180(1):141-55.
[23] Casamayor-Palleja M, Khan M, MacLennan IC. A subset of CD4+ memory T cells contains preformed CD40 ligand that is rapidly but transiently expressed on their surface after activation through the T cell receptor complex. J Exp Med. 1995;181(4):1293-301.
[24] Tong AW, Zhang BQ, Mues G, Solano M, Hanson T, Stone MJ. Anti-CD40 antibody binding modulates human multiple myeloma clonogenicity in vitro. Blood. 1994;84(9):3026-33.
[25] Urashima M, Chauhan D, Hatziyanni M, Ogata A, Hollenbaugh D, Aruffo A, Anderson KC. CD40 ligand triggers interleukin-6 mediated B cell differentiation. Leuk Res. 1996;20(6):507-15.
[26] Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994;76(2):275-85.
[27] Klein B, Zhang XG, Lu ZY, Bataille R. Interleukin-6 in human multiple myeloma. Blood. 1995;85(4):863-72.
[28] Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto K, Libermann TA, Anderson KC. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood. 1996;87(3):1104-12.
[29] Barill? S, Collette M, Bataille R, Amiot M. Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin. Blood. 1995;86(8):3151-9.
[30] Greipp PR. Advances in the diagnosis and management of myeloma. Semin Hematol. 1992;29(3 Suppl 2):24-45.
[31] Durie BG. Cellular and molecular genetic features of myeloma and related disorders. Hematol Oncol Clin North Am. 1992;6(2):463-77.
[32] Van Den Berghe H. Chromosomes in plasma-cell malignancies. Eur J Haematol Suppl. 1989;51:47-51.
[33] Cooper MR. A review of the clinical studies of alpha-interferon in the management of multiple myeloma. Semin Oncol. 1991;18(5 Suppl 7):18-29. 3
[34] Mendelsohn J, Howley PM, Israel M. The molecular basis of cancer. Philadelphia: W. B. Sounders co., 1995. 574 p.
[35] Portier M, Mol?s JP, Mazars GR, Jeanteur P, Bataille R, Klein B, Theillet C. p53 and RAS gene mutations in multiple myeloma. Oncogene. 1992;7(12):2539-43.
[36] Billadeau D, Jelinek DF, Shah N, LeBien TW, Van Ness B. Introduction of an activated N-ras oncogene alters the growth characteristics of the interleukin 6-dependent myeloma cell line ANBL6. Cancer Res. 1995;55(16):3640-6.
[37] Paquette RL, Berenson J, Lichtenstein A, McCormick F, Koeffler HP. Oncogenes in multiple myeloma: point mutation of N-ras. Oncogene. 1990;5(11):1659-63.
[38] Westendorf JJ, Lammert JM, Jelinek DF. Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines. Blood. 1995;85(12):3566-76.
[39] Raue F. Hypercalcemia of malignancy. Berlin: Springer, 1994. 163 p.
[40] Portier M, Zhang XG, Ursule E, Lees D, Jourdan M, Bataille R, Klein B. Cytokine gene expression in human multiple myeloma. Br J Haematol. 1993;85(3):514-20.
[41] Bataille R. Management of myeloma with bisphosphonates. N Engl J Med. 1996;334(8):529-30.
[42] Cozzolino F, Torcia M, Aldinucci D, Rubartelli A, Miliani A, Shaw AR, Lansdorp PM, Di Guglielmo R. Production of interleukin-1 by bone marrow myeloma cells. Blood. 1989;74(1):380-7.
[43] Diamant M, Hansen MB, Rieneck K, Svenson M, Yasukawa K, Bendtzen K. Differential interleukin-6 (IL-6) responses of three established myeloma cell lines in the presence of soluble human IL-6 receptors. Leuk Res. 1996;20(4):291-301.
[44] Cook G, Dumbar M, Franklin IM. The role of adhesion molecules in multiple myeloma. Acta Haematol. 1997;97(1-2):81-9.
[45] Merico F, Bergui L, Gregoretti MG, Ghia P, Aimo G, Lindley IJ, Caligaris-Cappio F. Cytokines involved in the progression of multiple myeloma. Clin Exp Immunol. 1993;92(1):27-31.
[46] Urashima M, Ogata A, Chauhan D, Hatziyanni M, Vidriales MB, Dedera DA, Schlossman RL, Anderson KC. Transforming growth factor-beta1: differential effects on multiple myeloma versus normal B cells. Blood. 1996;87(5):1928-38.
[47] Berg DJ, Lynch RG. Immune dysfunction in mice with plasmacytomas. I. Evidence that transforming growth factor-beta contributes to the altered expression of activation receptors on host B lymphocytes. J Immunol. 1991;146(8):2865-72.
[48] Kubagawa H, Vogler LB, Capra JD, Conrad ME, Lawton AR, Cooper MD. Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation. J Exp Med. 1979;150(4):792-807.
[49] Osterborg A, Steinitz M, Lewin N, Bergenbrant S, Holm G, Lefvert AK, Mellstedt H. Establishment of idiotype bearing B-lymphocyte clones from a patient with monoclonal gammopathy. Blood. 1991;78(10):2642-9.
[50] Corradini P, Boccadoro M, Voena C, Pileri A. Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas. J Exp Med. 1993;178(3):1091-6.
[51] Epstein J, Xiao HQ, He XY. Markers of multiple hematopoietic-cell lineages in multiple myeloma. N Engl J Med. 1990;322(10):664-8.
[52] Grogan TM, Durie BG, Spier CM, Richter L, Vela E. Myelomonocytic antigen positive multiple myeloma. Blood. 1989;73(3):763-9.
[53] Berenson J, Wong R, Kim K, Brown N, Lichtenstein A. Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma. Blood. 1987;70(5):1550-3.
[54] Van Riet I, Heirman C, Lacor P, De Waele M, Thielemans K, Van Camp B. Detection of monoclonal B lymphocytes in bone marrow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangement studies. Br J Haematol. 1989;73(3):289-95.
[55] Bakkus MH, Van Riet I, Van Camp B, Thielemans K. Evidence that the clonogenic cell in multiple myeloma originates from a pre-switched but somatically mutated B cell. Br J Haematol. 1994;87(1):68-74.
[56] Billadeau D, Ahmann G, Greipp P, Van Ness B. The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. J Exp Med. 1993;178(3):1023-31.
[57] Kampe CE, Hart S, Miller RA, Lichtenstein A, Kyle RA, Berenson JR. Expression of shared idiotypes by paraproteins from patients with monoclonal gammopathy of undetermined significance. Br J Haematol. 1994;87(4):719-24.
[58] King MA, Wells JV. Cell-bound immunoglobulin on peripheral blood mononuclear cells of patients with myeloma. Clin Exp Immunol. 1981;45(3):552-6.
[59] Berenson JR, Lichtenstein A, Hart S, Palomares D, Miller RA. Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance. Blood. 1990;75(11):2107-11.
[60] Kiyotaki M, Cooper MD, Bertoli LF, Kearney JF, Kubagawa H. Monoclonal anti-Id antibodies react with varying proportions of human B lineage cells. J Immunol. 1987;138(12):4150-8.
[61] Terstappen LW, Johnsen S, Segers-Nolten IM, Loken MR. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood. 1990;76(9):1739-47.
[62] *Vescio R, Hong C, Cao J, et al. Multiple myeloma clones are derived from post-class swith precursor cells. Blood. 1993; 82 (suppl. 1): 259a.
[63] Vescio RA, Cao J, Hong CH, Lee JC, Wu CH, Der Danielian M, Wu V, Newman R, Lichtenstein AK, Berenson JR. Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity. J Immunol. 1995;155(5):2487-97.
[64] Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991;66(4):663-74.
[65] Rabbitts TH. Chromosomal translocations in human cancer. Nature. 1994;372(6502):143-9.
[66] Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985;41(3):899-906.
[67] de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1982;300(5894):765-7.
[68] Urashima M, Ogata A, Chauhan D, Vidriales MB, Teoh G, Hoshi Y, Schlossman RL, DeCaprio JA, Anderson KC. Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein. Blood. 1996;88(6):2219-27.