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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 992-998
Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents apoptosis
Elizabeth E. Plowright,
Zhihua Li,
P. Leif Bergsagel,
Marta Chesi,
Dwayne L. Barber,
Donald R. Branch,
Robert G. Hawley, and
A.
Keith Stewart
From the Princess Margaret Hospital, Toronto, Ontario, Canada; and
Weill Medical College, Cornell University Medical School, New York, NY.
The t(4;14) translocation occurs in 25% of multiple myeloma (MM)
and results in both the ectopic expression of fibroblast growth factor
receptor 3 (FGFR3) from der4 and immunoglobulin heavy chain-MMSET
hybrid messenger RNA transcripts from der14. The subsequent selection
of activating mutations of the translocated FGFR3 by MM cells
indicates an important role for this signaling pathway in tumor
development and progression. To investigate the mechanism by which
FGFR3 overexpression promotes MM development, interleukin-6
(IL-6)-dependent murine B9 cells were transduced with retroviruses
expressing functional wild-type or constitutively activated mutant
FGFR3. Overexpression of mutant FGFR3 resulted in IL-6 independence,
decreased apoptosis, and an enhanced proliferative response to IL-6. In
the presence of ligand, wild-type FGFR3-expressing cells also exhibited
enhanced proliferation and survival in comparison to
controls. B9 clones expressing either wild-type FGFR3 at high levels or
mutant FGFR3 displayed increased phosphorylation of STAT3 and higher
levels of bcl-xL expression than did parental B9 cells
after cytokine withdrawal. The mechanism of the enhanced cell
responsiveness to IL-6 is unknown at this time, but does not
appear to be mediated by the mitogen-activated protein kinases SAPK,
p38, or ERK. These findings provide a rational explanation for the
mechanism by which FGFR3 contributes to both the viability and
propagation of the myeloma clone and provide a basis for the development of therapies targeting this pathway.
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29(1):
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|
|
|
|
|
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J. L.R. Brito, B. Walker, M. Jenner, N. J. Dickens, N. J.M. Brown, F. M. Ross, A. Avramidou, J. A.E. Irving, D. Gonzalez, F. E. Davies, et al.
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January 1, 2009;
94(1):
78 - 86.
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|
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|
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|
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J. L. Martinez-Torrecuadrada, L. H. Cheung, P. Lopez-Serra, R. Barderas, M. Canamero, S. Ferreiro, M. G. Rosenblum, and J. I. Casal
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7(4):
862 - 873.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
M. Sauvageau, M. Miller, S. Lemieux, J. Lessard, J. Hebert, and G. Sauvageau
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111(2):
790 - 799.
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|
|
|
|
|
|
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January 1, 2007;
2007(1):
298 - 327.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Masih-Khan, S. Trudel, C. Heise, Z. Li, J. Paterson, V. Nadeem, E. Wei, D. Roodman, J. O. Claudio, P. L. Bergsagel, et al.
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108(10):
3465 - 3471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pedranzini, T. Dechow, M. Berishaj, R. Comenzo, P. Zhou, J. Azare, W. Bornmann, and J. Bromberg
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66(19):
9714 - 9721.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W. Finch and J. S. Rubin
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J Natl Cancer Inst,
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98(12):
812 - 824.
[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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May 15, 2006;
107(10):
4039 - 4046.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Jaksic, S. Trudel, H. Chang, Y. Trieu, X. Qi, J. Mikhael, D. Reece, C. Chen, and A. K. Stewart
Clinical Outcomes in t(4;14) Multiple Myeloma: A Chemotherapy-Sensitive Disease Characterized by Rapid Relapse and Alkylating Agent Resistance
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October 1, 2005;
23(28):
7069 - 7073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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6280 - 6290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Constitutively activated FGFR3 mutants signal through PLC{gamma}-dependent and -independent pathways for hematopoietic transformation
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July 1, 2005;
106(1):
328 - 337.
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|
|
|
|
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|
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July 1, 2005;
106(1):
353 - 355.
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|
|
|
|
|
|
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4(5):
787 - 798.
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|
|
|
|
|
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April 1, 2005;
105(7):
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|
|
|
|
|
|
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|
|
|
|
|
|
|
A. M. Dring, F. E. Davies, J. A. L. Fenton, P. L. Roddam, K. Scott, D. Gonzalez, S. Rollinson, A. C. Rawstron, K. S. Rees-Unwin, C. Li, et al.
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10(17):
5692 - 5701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. Meyer, R. F. Gastwirt, D. D. Schlaepfer, and D. J. Donoghue
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279(27):
28450 - 28457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Trudel, S. Ely, Y. Farooqi, M. Affer, D. F. Robbiani, M. Chesi, and P. L. Bergsagel
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103(9):
3521 - 3528.
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[Full Text]
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|
|
|
|
|
|
|
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103(6):
2291 - 2298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Munshi, T. Hideshima, D. Carrasco, M. Shammas, D. Auclair, F. Davies, N. Mitsiades, C. Mitsiades, R. S. Kim, C. Li, et al.
Identification of genes modulated in multiple myeloma using genetically identical twin samples
Blood,
March 1, 2004;
103(5):
1799 - 1806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. N. Onwuazor, X.-Y. Wen, D.-Y. Wang, L. Zhuang, E. Masih-Khan, J. Claudio, B. Barlogie, J. D. Shaughnessy Jr, and A. K. Stewart
Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patients
Blood,
July 15, 2003;
102(2):
772 - 773.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. J. Elenitoba-Johnson, S. D. Jenson, R. T. Abbott, R. A. Palais, S. D. Bohling, Z. Lin, S. Tripp, P. J. Shami, L. Y. Wang, R. W. Coupland, et al.
Involvement of multiple signaling pathways in follicular lymphoma transformation: p38-mitogen-activated protein kinase as a target for therapy
PNAS,
June 10, 2003;
100(12):
7259 - 7264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Keats, T. Reiman, C. A. Maxwell, B. J. Taylor, L. M. Larratt, M. J. Mant, A. R. Belch, and L. M. Pilarski
In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression
Blood,
February 15, 2003;
101(4):
1520 - 1529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Anderson and W. S. Dalton
Synopsis of a Research Roundtable Presented on Cell Signaling in Myeloma: Regulation of Growth and Apoptosis--Opportunities for New Drug Discovery
Mol. Cancer Ther.,
December 1, 2002;
1(14):
1361 - 1365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Pollett, S. Trudel, D. Stern, Z. H. Li, and A. K. Stewart
Overexpression of the myeloma-associated oncogene fibroblast growth factor receptor 3 confers dexamethasone resistance
Blood,
November 15, 2002;
100(10):
3819 - 3821.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kong, C. S. Wang, and D. J. Donoghue
Interaction of Fibroblast Growth Factor Receptor 3 and the Adapter Protein SH2-B. A ROLE IN STAT5 ACTIVATION
J. Biol. Chem.,
May 3, 2002;
277(18):
15962 - 15970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guasch, V. Ollendorff, J.-P. Borg, D. Birnbaum, and M.-J. Pebusque
8p12 Stem Cell Myeloproliferative Disorder: the FOP-Fibroblast Growth Factor Receptor 1 Fusion Protein of the t(6;8) Translocation Induces Cell Survival Mediated by Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt/mTOR Pathways
Mol. Cell. Biol.,
December 1, 2001;
21(23):
8129 - 8142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Wang, R. P. Green, G. Zhao, and D. M. Ornitz
Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains
Development,
October 1, 2001;
128(19):
3867 - 3876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. De Vos, G. Couderc, K. Tarte, M. Jourdan, G. Requirand, M.-C. Delteil, J.-F. Rossi, N. Mechti, and B. Klein
Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays
Blood,
August 1, 2001;
98(3):
771 - 780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Li, Y. X. Zhu, E. E. Plowright, P. L. Bergsagel, M. Chesi, B. Patterson, T. S. Hawley, R. G. Hawley, and A. K. Stewart
The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells
Blood,
April 15, 2001;
97(8):
2413 - 2419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chesi, L. A. Brents, S. A. Ely, C. Bais, D. F. Robbiani, E. A. Mesri, W. M. Kuehl, and P. L. Bergsagel
Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma
Blood,
February 1, 2001;
97(3):
729 - 736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. Dalton, P. L. Bergsagel, W. M. Kuehl, K. C. Anderson, and J. L. Harousseau
Multiple Myeloma
Hematology,
January 1, 2001;
2001(1):
157 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Klasa, A. F. List, and B. D. Cheson
Rational Approaches to Design of Therapeutics Targeting Molecular Markers
Hematology,
January 1, 2001;
2001(1):
443 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. G. Willis and M. J. S. Dyer
The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies
Blood,
August 1, 2000;
96(3):
808 - 822.
[Full Text]
[PDF]
|
|
|
|
|
