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Blood, 15 January 2008, Vol. 111, No. 2, pp. 856-864. Prepublished online as a Blood First Edition Paper on October 17, 2007; DOI 10.1182/blood-2007-05-088674. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-05-088674v1 111/2/856    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 Lauring, J. Articles by Park, B. H. Search for Related Content PubMed PubMed Citation Articles by Lauring, J. Articles by Park, B. H. Related Collections Cell Cycle Cell Adhesion and Motility Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The multiple myeloma–associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity Josh Lauring1, Abde M. Abukhdeir1, Hiroyuki Konishi1, Joseph P. Garay1, John P. Gustin1,2, Qiuju Wang1, Robert J. Arceci1, William Matsui1, and Ben Ho Park1,2 1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, and 2 Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD Multiple myeloma (MM) is an incurable hematologic malignancy characterized by recurrent chromosomal translocations. Patients with t(4;14)(p16;q32) are the worst prognostic subgroup in MM, although the basis for this poor prognosis is unknown. The t(4;14) is unusual in that it involves 2 potential target genes: fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET). MMSET is universally overexpressed in t(4;14) MM, whereas FGFR3 expression is lost in one-third of cases. Nonetheless, the role of MMSET in t(4;14) MM has remained unclear. Here we demonstrate a role for MMSET in t(4;14) MM cells. Down-regulation of MMSET expression in MM cell lines by RNA interference and by selective disruption of the translocated MMSET allele using gene targeting dramatically reduced colony formation in methylcellulose but had only modest effects in liquid culture. In addition, MMSET knockdown led to cell-cycle arrest of adherent MM cells and reduced the ability of MM cells to adhere to extracellular matrix. Finally, MMSET knockdown and knockout reduced tumor formation by MM xenografts. These results provide the first direct evidence that MMSET plays a significant role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Marango, M. Shimoyama, H. Nishio, J. A. Meyer, D.-J. Min, A. Sirulnik, Y. Martinez-Martinez, M. Chesi, P. L. Bergsagel, M.-M. Zhou, et al. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor Blood, March 15, 2008; 111(6): 3145 - 3154. [Abstract] [Full Text] [PDF]

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