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Blood, 1 August 2004, Vol. 104, No. 3, pp. 607-618. Prepublished online as a Blood First Edition Paper on April 15, 2004; DOI 10.1182/blood-2004-01-0037. This Article Full Text (PDF) All Versions of this Article: 2004-01-0037v1 104/3/607    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hideshima, T. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Hideshima, T. Articles by Anderson, K. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 9, 2004 Accepted March 26, 2004 Advances in Biology of Multiple Myeloma: Clinical Applications Teru Hideshima, P L Bergsagel, W M Kuehl, and Kenneth C Anderson* Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Weill Medical College of Cornell University, New York, NY, USA Genetics Branch, National Cancer Institute, Bethesda, MD, USA * Corresponding author; email: kenneth_anderson{at}dfci.harvard.edu. There appear to be two pathways involved in the early pathogenesis of premalignant monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) tumors. Nearly half of these tumors are non-hyperdiploid and mostly have IgH translocations that involve five recurrent chromosomal loci, including 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (FGFR3 & MMSET), 16q23 (c-maf), and 20q11 (mafB). The remaining tumors are hyperdiploid and contain multiple trisomies involving chromosomes 3,5,7,9,11,15,19, and 21, but infrequently have IgH translocations involving the five recurrent loci. Dysregulated expression of cyclin D1, D2, or D3 appears to occur as an early event in virtually all of these tumors. This may render the cells more susceptible to proliferative stimuli, resulting in selective expansion as a result of interaction with bone marrow stromal cells that produce IL-6 and other cytokines. Five proposed tumor groups, defined by IgH translocations and/or cyclin D expression, appear to have differences in biological properties, including interaction with stromal cells, prognosis and response to specific therapies. Delineation of the mechanisms mediating MM cell proliferation, survival, and migration in the bone marrow (BM) microenvironment may both enhance understanding of pathogenesis and provide the framework for identification and validation of novel molecular targets. 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FTY720 Induces Apoptosis in Multiple Myeloma Cells and Overcomes Drug Resistance Cancer Res., August 15, 2005; 65(16): 7478 - 7484. [Abstract] [Full Text] [PDF] J. Moreaux, F. W. Cremer, T. Reme, M. Raab, K. Mahtouk, P. Kaukel, V. Pantesco, J. De Vos, E. Jourdan, A. Jauch, et al. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature Blood, August 1, 2005; 106(3): 1021 - 1030. [Abstract] [Full Text] [PDF] N. Raje, S. Kumar, T. Hideshima, A. Roccaro, K. Ishitsuka, H. Yasui, N. Shiraishi, D. Chauhan, N. C. Munshi, S. R. Green, et al. Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma Blood, August 1, 2005; 106(3): 1042 - 1047. [Abstract] [Full Text] [PDF] H. Yasui, T. Hideshima, M. Hamasaki, A. M. Roccaro, N. Shiraishi, S. Kumar, P. Tassone, K. Ishitsuka, N. Raje, Y.-T. Tai, et al. SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma Blood, July 15, 2005; 106(2): 706 - 712. [Abstract] [Full Text] [PDF] O. Goker-Alpan and E. Sidransky Risky business: Gaucher disease and multiple myeloma Blood, June 15, 2005; 105(12): 4546 - 4547. [Full Text] [PDF] M. Ladetto, S. Vallet, A. Trojan, M. Dell'Aquila, L. Monitillo, R. Rosato, L. Santo, D. Drandi, A. Bertola, P. Falco, et al. Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome Blood, June 15, 2005; 105(12): 4784 - 4791. [Abstract] [Full Text] [PDF] M. Hamasaki, T. Hideshima, P. Tassone, P. Neri, K. Ishitsuka, H. Yasui, N. Shiraishi, N. Raje, S. Kumar, D. H. Picker, et al. Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo Blood, June 1, 2005; 105(11): 4470 - 4476. [Abstract] [Full Text] [PDF] X. Carvajal-Vergara, S. Tabera, J. C. Montero, A. Esparis-Ogando, R. Lopez-Perez, G. Mateo, N. Gutierrez, M. Parmo-Cabanas, J. Teixido, J. F. San Miguel, et al. Multifunctional role of Erk5 in multiple myeloma Blood, June 1, 2005; 105(11): 4492 - 4499. [Abstract] [Full Text] [PDF] K. Ito, T. Nakazato, M. J. Xian, T. Yamada, N. Hozumi, A. Murakami, H. Ohigashi, Y. Ikeda, and M. Kizaki 1'-Acetoxychavicol Acetate Is a Novel Nuclear Factor {kappa}B Inhibitor with Significant Activity against Multiple Myeloma In vitro and In vivo Cancer Res., May 15, 2005; 65(10): 4417 - 4424. [Abstract] [Full Text] [PDF] F.-J. Li, N. Tsuyama, H. Ishikawa, M. Obata, S. Abroun, S. Liu, K.-i. Otsuyama, X. Zheng, Z. Ma, Y. Maki, et al. 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