Best Practice & Research Clinical Haematology
Volume 20, Issue 4 , Pages 597-612 , December 2007

The malignant clone and the bone-marrow environment

References 

  1. Bergsagel PL, Kuehl WM, Zhan F, et al. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106:296–303
  2. Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998;91:3–21
  3. Kyle RA, Beard CM, O'Fallon WM, et al. Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945. Journal of Clinical Oncology. 1994;12:1577–1583
  4. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. The New England Journal of Medicine. 2002;346:564–569
  5. Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nature Reviews. Cancer. 2002;2:175–187
  6. Fonseca R, Debes-Marun CS, Picken EB, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003;102:2562–2567
  7. Smadja NV, Bastard C, Brigaudeau C, et al. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98:2229–2238
  8. Smadja NV, Leroux D, Soulier J, et al. Further cytogenetic characterization of multiple myeloma confirms that 14q32 translocations are a very rare event in hyperdiploid cases. Genes, Chromosomes & Cancer. 2003;38:234–239
  9. Avet-Loiseau H, Facon T, Daviet A, 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 Research. 1999;59:4546–4550
  10. Bergsagel PL, Kuehl WM. Chromosome translocations in multiple myeloma. Oncogene. 2001;20:5611–5622
  11. Chesi M, Brents LA, Ely SA, et al. Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma. Blood. 2001;97:729–736
  12. Li Z, Zhu YX, Plowright EE, et al. The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells. Blood. 2001;97:2413–2419
  13. Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101:4569–4575
  14. Keats JJ, Reiman T, Maxwell CA, et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood. 2003;101:1520–1529
  15. Moreau P, Facon T, Leleu X, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood. 2002;100:1579–1583
  16. Grand EK, Chase AJ, Heath C, et al. Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia. 2004;18:962–966
  17. Chen J, Lee BH, Williams IR, et al. FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. Oncogene. 2005;24:8259–8267
  18. Trudel S, Li ZH, Wei E, et al. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005;105:2941–2948
  19. Hurt EM, Wiestner A, Rosenwald A, 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;5:191–199
  20. Avet-Loiseau H, Gerson F, Magrangeas F, et al. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood. 2001;98:3082–3086
  21. Shou Y, Martelli ML, Gabrea A, et al. Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. Proceedings of the National Academy of Sciences of the United States of America. 2000;97:228–233
  22. Cheung WC, Kim JS, Linden M, et al. Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. The Journal of Clinical Investigation. 2004;113:1763–1773
  23. Bezieau S, Devilder MC, Avet-Loiseau H, et al. High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis. Human Mutation. 2001;18:212–224
  24. Liu P, Leong T, Quam L, et al. Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial. Blood. 1996;88:2699–2706
  25. Drach J, Ackermann J, Fritz E, et al. Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy. Blood. 1998;92:802–809
  26. Juge-Morineau N, Harousseau JL, Amiot M, et al. The retinoblastoma susceptibility gene RB-1 in multiple myeloma. Leukemia & Lymphoma. 1997;24:229–237
  27. Kulkarni MS, Daggett JL, Bender TP, et al. Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis. Leukemia. 2002;16:127–134
  28. Fonseca R, Bailey RJ, Ahmann GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002;100:1417–1424
  29. Shapiro-Shelef M, Calame K. Plasma cell differentiation and multiple myeloma. Current Opinion in Immunology. 2004;16:226–234
  30. Gyory I, Fejer G, Ghosh N, et al. Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines. Journal of Immunology. 2003;170:3125–3133
  31. Chim CS, Fung TK, Cheung WC, et al. SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the Jak/STAT pathway. Blood. 2004;103:4630–4635
  32. Wu KD, Orme LM, Shaughnessy J, et al. Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival. Blood. 2003;101:4982–4989
  33. Shammas MA, Shmookler Reis RJ, Akiyama M, et al. Telomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma. Molecular Cancer Therapeutics. 2003;2:825–833
  34. Akiyama M, Hideshima T, Hayashi T, et al. Cytokines modulate telomerase activity in a human multiple myeloma cell line. Cancer Research. 2002;62:3876–3882
  35. Akiyama M, Hideshima T, Hayashi T, et al. Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Research. 2003;63:18–21
  36. Maser RS, DePinho RA. Connecting chromosomes, crisis, and cancer. Science. 2002;297:565–569
  37. Akiyama M, Hideshima T, Munshi NC, et al. Telomerase inhibitors as anticancer therapy. Current Medicinal Chemistry. Anti-cancer Agents. 2002;2:567–575
  38. Davies FE, Dring AM, Li C, et al. Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood. 2003;102:4504–4511
  39. Hideshima T, Bergsagel PL, Kuehl WM, et al. Advances in biology of multiple myeloma: clinical applications. Blood. 2004;104:607–618
  40. Chatterjee M, Honemann D, Lentzsch S, et al. In the presence of bone marrow stromal cells human multiple myeloma cells become independent of the IL-6/gp130/STAT3 pathway. Blood. 2002;100:3311–3318
  41. Jensen GS, Belch AR, Mant MJ, et al. Expression of multiple beta 1 integrins on circulating monoclonal B cells in patients with multiple myeloma. American Journal of Hematology. 1993;43:29–36
  42. Damiano JS, Cress AE, Hazlehurst LA, et al. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93:1658–1667
  43. Vacca A, Ria R, Presta M, et al. Alpha(v)beta(3) integrin engagement modulates cell adhesion, proliferation, and protease secretion in human lymphoid tumor cells. Experimental Hematology. 2001;29:993–1003
  44. Ria R, Vacca A, Ribatti D, et al. Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma. Haematologica. 2002;87:836–845
  45. Uchiyama H, Barut BA, Chauhan D, et al. Characterization of adhesion molecules on human myeloma cell lines. Blood. 1992;80:2306–2314
  46. Uchiyama H, Barut BA, Mohrbacher AF, et al. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood. 1993;82:3712–3720
  47. Hazlehurst LA, Damiano JS, Buyuksal I, et al. Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene. 2000;19:4319–4327
  48. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98:210–216
  49. Hayashi T, Hideshima T, Akiyama M, et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. British Journal of Haematology. 2005;128:192–203
  50. Bellucci R, Alyea EP, Weller E, et al. Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma. Blood. 2002;99:4610–4617
  51. Bellucci R, Wu CJ, Chiaretti S, et al. Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens. Blood. 2004;103:656–663
  52. Raje N, Hideshima T, Davies FE, et al. Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma. British Journal of Haematology. 2004;125:343–352
  53. Vasir B, Borges V, Wu Z, et al. Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation. British Journal of Haematology. 2005;129:687–700
  54. LeBlanc R, Hideshima T, Catley LP, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2004;103:1787–1790
  55. Prabhala RH, Neri P, Bae JE, et al. Dysfunctional T regulatory cells in multiple myeloma. Blood. 2006;107:301–304
  56. Stevenson FK, Anderson KC. Immunotherapy for multiple myeloma: insights from other models. Leukemia Research. 2002;26:403–405
  57. Stevenson FK, Anderson KC. Preparing the ground for vaccination against multiple myeloma. Immunology Today. 2000;21:170–171
  58. Tai YT, Li XF, Breitkreutz I, et al. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Research. 2006;66:6675–6682
  59. Podar K, Hideshima T, Chauhan D, et al. Targeting signalling pathways for the treatment of multiple myeloma. Expert Opinion on Therapeutic Targets. 2005;9:359–381
  60. Giuliani N, Rizzoli V, Roodman GD. Multiple myeloma bone disease: pathophysiology of osteoblast inhibition. Blood. 2006;108:3992–3996
  61. Ruscetti FW. Hematologic effects of interleukin-1 and interleukin-6. Current Opinion in Hematology. 1994;1:210–215
  62. 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
  63. Gado K, Domjan G, Hegyesi H, et al. Role of INTERLEUKIN-6 in the pathogenesis of multiple myeloma. Cell Biology International. 2000;24:195–209
  64. Urashima M, Chauhan D, Uchiyama H, et al. CD40 ligand triggered interleukin-6 secretion in multiple myeloma. Blood. 1995;85:1903–1912
  65. Tai YT, Podar K, Gupta D, et al. CD40 activation induces p53-dependent vascular endothelial growth factor secretion in human multiple myeloma cells. Blood. 2002;99:1419–1427
  66. Hideshima T, Chauhan D, Schlossman R, et al. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001;20:4519–4527
  67. Costes V, Portier M, Lu ZY, et al. Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production. British Journal of Haematology. 1998;103:1152–1160
  68. Lust JA, Donovan KA. The role of interleukin-1 beta in the pathogenesis of multiple myeloma. Hematology/Oncology Clinics of North America. 1999;13:1117–1125
  69. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380:439–442
  70. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–439
  71. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376:62–66
  72. Gerber HP, Malik AK, Solar GP, et al. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 2002;417:954–958
  73. Gabrilovich DI, Chen HL, Girgis KR, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nature Medicine. 1996;2:1096–1103
  74. Henriksen K, Karsdal M, Delaisse JM, et al. RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism. The Journal of Biological Chemistry. 2003;278:48745–48753
  75. Midy V, Plouet J. Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochemical and Biophysical Research Communications. 1994;199:380–386
  76. Melder RJ, Koenig GC, Witwer BP, et al. During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Nature Medicine. 1996;2:992–997
  77. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine. 2001;7:1194–1201
  78. Podar K, Tai YT, Davies FE, et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood. 2001;98:428–435
  79. Vincent L, Jin DK, Karajannis MA, et al. Fetal stromal-dependent paracrine and intracrine vascular endothelial growth factor-a/vascular endothelial growth factor receptor-1 signaling promotes proliferation and motility of human primary myeloma cells. Cancer Research. 2005;65:3185–3192
  80. Ferlin M, Noraz N, Hertogh C, et al. Insulin-like growth factor induces the survival and proliferation of myeloma cells through an interleukin-6-independent transduction pathway. British Journal of Haematology. 2000;111:626–634
  81. Tu Y, Gardner A, Lichtenstein A. The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses. Cancer Research. 2000;60:6763–6770
  82. Qiang YW, Kopantzev E, Rudikoff S. Insulinlike growth factor-I signaling in multiple myeloma: downstream elements, functional correlates, and pathway cross-talk. Blood. 2002;99:4138–4146
  83. Qiang YW, Yao L, Tosato G, et al. Insulin-like growth factor I induces migration and invasion of human multiple myeloma cells. Blood. 2004;103:301–308
  84. Ge NL, Rudikoff S. Insulin-like growth factor I is a dual effector of multiple myeloma cell growth. Blood. 2000;96:2856–2861
  85. Tai YT, Podar K, Catley L, et al. Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta1-integrin and phosphatidylinositol 3′-kinase/AKT signaling. Cancer Research. 2003;63:5850–5858
  86. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell. 2004;5:221–230
  87. Hideshima T, Chauhan D, Hayashi T, et al. The biological sequelae of stromal cell-derived factor-1alpha in multiple myeloma. Molecular Cancer Therapeutics. 2002;1:539–544
  88. Lentzsch S, Gries M, Janz M, et al. Macrophage inflammatory protein 1-alpha (MIP-1 alpha) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells. Blood. 2003;101:3568–3573
  89. Lentzsch S, Chatterjee M, Gries M, et al. PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells. Leukemia. 2004;18:1883–1890
  90. Mahtouk K, Jourdan M, De Vos J, et al. An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis. Blood. 2004;103:1829–1837
  91. Tavassoli M. Structure and function of sinusoidal endothelium of bone marrow. Progress in Clinical and Biological Research. 1981;59B:249–256
  92. Rafii S, Mohle R, Shapiro F, et al. Regulation of hematopoiesis by microvascular endothelium. Leukemia & Lymphoma. 1997;27:375–386
  93. Rafii S, Shapiro F, Rimarachin J, et al. Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion. Blood. 1994;84:10–19
  94. Mohle R, Green D, Moore MA, et al. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proceedings of the National Academy of Sciences of the United States of America. 1997;94:663–668
  95. Avecilla ST, Hattori K, Heissig B, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Medicine. 2004;10:64–71
  96. Choi K, Kennedy M, Kazarov A, et al. A common precursor for hematopoietic and endothelial cells. Development. 1998;125:725–732
  97. Nishikawa SI. A complex linkage in the developmental pathway of endothelial and hematopoietic cells. Current Opinion in Cell Biology. 2001;13:673–678
  98. Podar K, Anderson KC. The pathophysiological role of VEGF in hematological malignancies: therapeutic implications. Blood. 2005;105:1383–1395
  99. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. The New England Journal of Medicine. 1999;341:1565–1571
  100. Rajkumar SV, Hayman S, Gertz MA, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. Journal of Clinical Oncology. 2002;20:4319–4323
  101. Weber D, Rankin K, Gavino M, et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. Journal of Clinical Oncology. 2003;21:16–19
  102. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825–831
  103. Palumbo A, Ambrosini MT, Benevolo G, et al. Bortezomib, melphalan, prednisone and thalidomide for relapsed multiple myeloma. Blood. 2007;109:2767–2772
  104. Vacca A, Ria R, Semeraro F, et al. Endothelial cells in the bone marrow of patients with multiple myeloma. Blood. 2003;102:3340–3348
  105. Pellegrino A, Ria R, Pietro GD, et al. Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells. British Journal of Haematology. 2005;129:248–256
  106. Lin B, Podar K, Gupta D, et al. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. Cancer Research. 2002;62:5019–5026
  107. Podar K, Tonon G, Sattler M, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proceedings of the National Academy of Sciences of the United States of America. 2006;103:19478–19483
  108. Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nature Reviews. Drug Discovery. 2004;3:391–400
  109. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. The New England Journal of Medicine. 2004;350:2335–2342
  110. Sandler A, Gray R, Perry MC. et al Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. The New England Journal of Medicine. 2006;355:2542–2550
  111. Zhang H, Vakil V, Braunstein M, et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005;105:3286–3294
  112. Podar K, Anderson KC. Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies. Cell Cycle. 2007;6:538–542
  113. Yaccoby S, Pearse RN, Johnson CL, et al. Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. British Journal of Haematology. 2002;116:278–290
  114. Vanderkerken K, De Leenheer E, Shipman C, et al. Recombinant osteoprotegerin decreases tumor burden and increases survival in a murine model of multiple myeloma. Cancer Research. 2003;63:287–289
  115. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. The New England Journal of Medicine. 1996;334:488–493
  116. Dhodapkar MV, Singh J, Mehta J, et al. Anti-myeloma activity of pamidronate in vivo. British Journal of Haematology. 1998;103:530–532
  117. Han JH, Choi SJ, Kurihara N, et al. Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood. 2001;97:3349–3353
  118. Masih-Khan E, Trudel S, Heise C, et al. MIP-1{alpha} (CCL3) is a downstream target of FGFR3 and RAS/MAPK signaling in multiple myeloma. Blood. 2006;
  119. Choi SJ, Cruz JC, Craig F, et al. Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood. 2000;96:671–675
  120. Choi SJ, Oba Y, Gazitt Y, et al. Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. The Journal of Clinical Investigation. 2001;108:1833–1841
  121. Oyajobi BO, Franchin G, Williams PJ, et al. Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood. 2003;102:311–319
  122. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–176
  123. Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proceedings of the National Academy of Sciences of the United States of America. 1999;96:3540–3545
  124. Bucay N, Sarosi I, Dunstan CR, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes & Development. 1998;12:1260–1268
  125. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397:315–323
  126. Farrugia AN, Atkins GJ, To LB, et al. Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Research. 2003;63:5438–5445
  127. Heider U, Langelotz C, Jakob C, et al. Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Clinical Cancer Research. 2003;9:1436–1440
  128. Roux S, Meignin V, Quillard J, et al. RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma. British Journal of Haematology. 2002;117:86–92
  129. Giuliani N, Bataille R, Mancini C, et al. Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood. 2001;98:3527–3533
  130. Pearse RN, Sordillo EM, Yaccoby S, et al. Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proceedings of the National Academy of Sciences of the United States of America. 2001;98:11581–11586
  131. Giuliani N, Colla S, Sala R, et al. Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood. 2002;100:4615–4621
  132. Standal T, Seidel C, Hjertner O, et al. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood. 2002;100:3002–3007
  133. Croucher PI, Shipman CM, Lippitt J, et al. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood. 2001;98:3534–3540
  134. Body JJ, Greipp P, Coleman RE, et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer. 2003;97:887–892
  135. Komori T. Regulation of skeletal development by the Runx family of transcription factors. Journal of Cellular Biochemistry. 2005;95:445–453
  136. Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755–764
  137. Giuliani N, Colla S, Morandi F, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood. 2005;106:2472–2483
  138. Thirunavukkarasu K, Halladay DL, Miles RR, et al. The osteoblast-specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function. The Journal of Biological Chemistry. 2000;275:25163–25172
  139. Tian E, Zhan F, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. The New England Journal of Medicine. 2003;349:2483–2494
  140. Terpos E, Heath DJ, Rahemtulla A, et al. Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. British Journal of Haematology. 2006;135:688–692
  141. Politou MC, Heath DJ, Rahemtulla A, et al. Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. International Journal of Cancer. 2006;119:1728–1731
  142. Oshima T, Abe M, Asano J, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood. 2005;106:3160–3165
  143. Lee JW, Chung HY, Ehrlich LA, et al. IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood. 2004;103:2308–2315
  144. Ehrlich LA, Chung HY, Ghobrial I, et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood. 2005;106:1407–1414
  145. Giuliani N, Morandi F, Tagliaferri S, et al. Interleukin-3 (IL-3) is overexpressed by T lymphocytes in multiple myeloma patients. Blood. 2006;107:841–842
  146. Colucci S, Brunetti G, Rizzi R, et al. T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction. Blood. 2004;104:3722–3730
  147. Theocharis AD, Seidel C, Borset M, et al. Serglycin constitutively secreted by myeloma plasma cells is a potent inhibitor of bone mineralization in vitro. The Journal of Biological Chemistry. 2006;
  148. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–841
  149. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–846
  150. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004;116:769–778
  151. Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science. 2000;287:1427–1430

PII: S1521-6926(07)00063-1

doi: 10.1016/j.beha.2007.08.002

Best Practice & Research Clinical Haematology
Volume 20, Issue 4 , Pages 597-612 , December 2007