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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 (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 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 Social Bookmarking                   What's this? Submitted February 25, 2002 Accepted April 18, 2002 Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 (FGFR3) confers dexamethasone resistance Jonathan B Pollett, Suzanne Trudel, Daniel Stern, Zhihua Li, and A K Stewart* Division of Experimental Therapeutics, Toronto General Research Institute, Toronto, ON, Canada Division of Experimental Therapeutics, Toronto General Research Institute, Toronto, ON, Canada; Department of Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada * Corresponding author; email: kstewart{at}uhnres.utoronto.ca. Translocations involving the immunoglobulin heavy chain switch region and fibroblast growth factor receptor 3 (FGFR3) are identified in 10-15% of myeloma patients. In previous work we over expressed 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 now tested FGFR3-expressing B9 cells for chemotherapy sensitivity. FGFR3 expression did not alter sensitivity to Melphalan or Doxorubicin. In contrast, B9 cells over expressing FGFR3 were resistant to treatment with Dexamethasone, a phenomenon successfully reversed using a Bcl-xL anti-sense oligonucleotide. This data thus demonstrates that overexpression of FGFR3 in B9 cells confers resistance to Dexamethasone, but not to anthracyclines or alkylating agents, at least in part through the upregulation of Bcl-xL. This finding has potential implications for the use of chemotherapy in t(4;14)-positive myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Salazar, T. Kashiwada, P. Krejci, P. Muchowski, D. Donoghue, W. R. Wilcox, and L. M. 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