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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2020-2028. Prepublished online as a Blood First Edition Paper on May 25, 2006; DOI 10.1182/blood-2005-11-013458. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2005-11-013458v1 108/6/2020    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Zhan, F. Articles by Shaughnessy, J. D. Search for Related Content PubMed PubMed Citation Articles by Zhan, F. Articles by Shaughnessy, J. D., Jr Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The molecular classification of multiple myeloma Fenghuang Zhan, Yongsheng Huang, Simona Colla, James P. Stewart, Ichiro Hanamura, Sushil Gupta, Joshua Epstein, Shmuel Yaccoby, Jeffrey Sawyer, Bart Burington, Elias Anaissie, Klaus Hollmig, Mauricio Pineda-Roman, Guido Tricot, Frits van Rhee, Ronald Walker, Maurizio Zangari, John Crowley, Bart Barlogie, and John D. Shaughnessy, Jr From the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, the Myeloma Institute for Research and Therapy, the Department of Pathology, and the Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR; and Cancer Research and Biostatistics, Seattle, WA. To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF– and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L.R. Brito, B. Walker, M. Jenner, N. J. Dickens, N. J.M. Brown, F. M. Ross, A. Avramidou, J. A.E. Irving, D. Gonzalez, F. E. Davies, et al. 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Russell, S. R. Hayman, et al. Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement Mayo Clin. Proc., March 1, 2007; 82(3): 323 - 341. [Abstract] [Full Text] [PDF] S. Yaccoby, W. Ling, F. Zhan, R. Walker, B. Barlogie, and J. D. Shaughnessy Jr Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo Blood, March 1, 2007; 109(5): 2106 - 2111. [Abstract] [Full Text] [PDF] F. Zhan, B. Barlogie, V. Arzoumanian, Y. Huang, D. R. Williams, K. Hollmig, M. Pineda-Roman, G. Tricot, F. van Rhee, M. Zangari, et al. Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis Blood, February 15, 2007; 109(4): 1692 - 1700. [Abstract] [Full Text] [PDF] L. Agnelli, S. Bicciato, S. Fabris, L. Baldini, F. Morabito, D. Intini, D. Verdelli, A. Callegaro, F. Bertoni, G. Lambertenghi-Deliliers, et al. 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