TY - JOUR
T1 - Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 confers dexamethasone resistance
AU - Pollett, Jonathan B.
AU - Trudel, Suzanne
AU - Stern, Daniel
AU - Li, Zhixiong H.
AU - Keith Stewart, A.
PY - 2002/11/15
Y1 - 2002/11/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2002-02-0608
DO - 10.1182/blood-2002-02-0608
M3 - Article
C2 - 12393593
AN - SCOPUS:0037111779
SN - 0006-4971
VL - 100
SP - 3819
EP - 3821
JO - Blood
JF - Blood
IS - 10
ER -