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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-02-0608. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-02-0608v1 100/10/3819    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 Pollett, J. B. Articles by Stewart, A. K. Search for Related Content PubMed PubMed Citation Articles by Pollett, J. B. Articles by Stewart, A. K. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2002, Vol. 100, No. 10, pp. 3819-3821 BRIEF REPORT Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 confers dexamethasone resistance Jonathan B. Pollett, Suzanne Trudel, Daniel Stern, Zhixiong H. Li, and A. Keith Stewart From the Division of Experimental Therapeutics, Toronto General Research Institute, and the Department of Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada. Translocations involving the immunoglobulin heavy-chain switch region and fibroblast growth factor receptor 3 (FGFR3) are identified in 10% to 15% of patients with myeloma. In previous research we overexpressed FGFR3 or the constitutively active FGFR3-TD mutant in an interleukin-6 (IL-6)-dependent murine myeloma cell line, B9. FGFR3-enhanced IL-6 responsiveness increased phosphorylation of STAT3 and up-regulated Bcl-xL. Since Bcl-xL was up-regulated, we have tested FGFR3-expressing B9 cells for chemotherapy sensitivity. FGFR3 expression did not alter sensitivity to melphalan or doxorubicin. In contrast, B9 cells overexpressing FGFR3 were resistant to treatment with dexamethasone, a phenomenon successfully reversed using a Bcl-xL antisense oligonucleotide. These data demonstrate that the overexpression of FGFR3 in B9 cells confers resistance to dexamethasone but not to anthracyclines or alkylating agents, at least in part through the up-regulation of Bcl-xL. This finding has potential implications for the use of chemotherapy in t(4;14)-positive myeloma. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-T. Tai, M. Fulciniti, T. Hideshima, W. Song, M. Leiba, X.-F. Li, M. Rumizen, P. Burger, A. Morrison, K. Podar, et al. Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis Blood, September 1, 2007; 110(5): 1656 - 1663. [Abstract] [Full Text] [PDF] S. Trudel, A. K. Stewart, Z. Li, Y. Shu, S.-B. Liang, Y. Trieu, D. Reece, J. Paterson, D. Wang, and X.-Y. Wen The Bcl-2 Family Protein Inhibitor, ABT-737, Has Substantial Antimyeloma Activity and Shows Synergistic Effect with Dexamethasone and Melphalan Clin. Cancer Res., January 15, 2007; 13(2): 621 - 629. [Abstract] [Full Text] [PDF] A. M. Monjazeb, K. P. High, A. Connoy, L. S. Hart, C. Koumenis, and F. H. Chilton Arachidonic acid-induced gene expression in colon cancer cells Carcinogenesis, October 1, 2006; 27(10): 1950 - 1960. [Abstract] [Full Text] [PDF] S. Trudel, A. K. Stewart, E. Rom, E. Wei, Z. H. Li, S. Kotzer, I. Chumakov, Y. Singer, H. Chang, S.-B. Liang, et al. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020