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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 (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 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 Social Bookmarking                   What's this? Submitted October 24, 2003 Accepted December 23, 2003 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 Peter L Bergsagel* Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA Immunology Program, Graduate School of Medical Sciences of Cornell University, New York, NY, USA; Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA; Immunology Program, Graduate School of Medical Sciences of Cornell University, New York, NY, USA * Corresponding author; email: plbergsa{at}med.cornell.edu. 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 PD173074 treated mice. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. St-Germain, P. Taylor, J. Tong, L. L. Jin, A. Nikolic, I. I. Stewart, R. M. Ewing, M. Dharsee, Z. Li, S. Trudel, et al. Multiple myeloma phosphotyrosine proteomic profile associated with FGFR3 expression, ligand activation, and drug inhibition PNAS, November 24, 2009; 106(47): 20127 - 20132. [Abstract] [Full Text] [PDF] L. Salazar, T. Kashiwada, P. Krejci, P. Muchowski, D. Donoghue, W. R. Wilcox, and L. M. 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