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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3521-3528. Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-10-3650. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3650v1 103/9/3521    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 Trudel, S. Articles by Bergsagel, P. L. Search for Related Content PubMed PubMed Citation Articles by Trudel, S. Articles by Bergsagel, P. L. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma Suzanne Trudel, Scott Ely, Yildiz Farooqi, Maurizio Affer, Davide F. Robbiani, Marta Chesi, and P. Leif Bergsagel From the Departments of Medicine and Pathology, and Immunology Program, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY. We have previously shown that dysregulation of fibroblast growth factor receptor 3 (FGFR3) by the t(4;14) translocation is a primary event in multiple myeloma (MM) and that activating mutations of FGFR3 are acquired in some cases. We describe here inhibition of wild-type (WT) and constitutively activated mutant FGFR3 autophosphorylation by the small molecule inhibitor, PD173074. Inhibition of FGFR3 in human myeloma cell lines was associated with decreased viability and tumor cell growth arrest. Further, morphologic, phenotypic, and functional changes typical of plasma cell (PC) differentiation, including increase in light-chain secretion and expression of CD31, were observed and this was followed by apoptosis. Finally, using a mouse model of FGFR3 myeloma, we demonstrate a delay in tumor progression and prolonged survival of mice treated with PD173074. These results indicate that inhibition of FGFR3, even in advanced disease associated with multiple genetic changes, may allow the cell to complete its developmental program and render it sensitive to apoptotic signals. In addition, this represents the validation of a therapeutic target in MM that may benefit patients who have a very poor prognosis with currently available treatments. (Blood. 2004;103:3521-3528) 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. Thompson A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells Hum. Mol. Genet., June 1, 2009; 18(11): 1951 - 1961. [Abstract] [Full Text] [PDF] S. Kang, S. Elf, S. Dong, T. Hitosugi, K. Lythgoe, A. Guo, H. Ruan, S. Lonial, H. J. Khoury, I. R. Williams, et al. Fibroblast Growth Factor Receptor 3 Associates with and Tyrosine Phosphorylates p90 RSK2, Leading to RSK2 Activation That Mediates Hematopoietic Transformation Mol. Cell. Biol., April 15, 2009; 29(8): 2105 - 2117. [Abstract] [Full Text] [PDF] A. Roidl, H.-J. Berger, S. Kumar, J. Bange, P. Knyazev, and A. Ullrich Resistance to Chemotherapy Is Associated with Fibroblast Growth Factor Receptor 4 Up-Regulation Clin. Cancer Res., March 15, 2009; 15(6): 2058 - 2066. 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