Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 confers dexamethasone resistance

Jonathan B. Pollett, Suzanne Trudel, Daniel Stern, Zhixiong H. Li, A. Keith Stewart

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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-X L. Since Bcl-X L 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-X L 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-X L. This finding has potential implications for the use of chemotherapy in t(4;14)-positive myeloma.

Original languageEnglish (US)
Pages (from-to)3819-3821
Number of pages3
JournalBlood
Volume100
Issue number10
DOIs
StatePublished - Nov 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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