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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1374-1376. Prepublished online as a Blood First Edition Paper on April 27, 2006; DOI 10.1182/blood-2006-02-004457. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-004457v1 108/4/1374    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 Lierman, E. Articles by Cools, J. Search for Related Content PubMed PubMed Citation Articles by Lierman, E. Articles by Cools, J. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Sorafenib is a potent inhibitor of FIP1L1-PDGFR and the imatinib-resistant FIP1L1-PDGFR T674I mutant Els Lierman, Cedric Folens, Elizabeth H. Stover, Nicole Mentens, Helen Van Miegroet, Werner Scheers, Marc Boogaerts, Peter Vandenberghe, Peter Marynen, and Jan Cools From the Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), the Department of Hematology, Universitaire Ziekenhuizen (UZ) Leuven, and the Department of Human Genetics, University of Leuven, Belgium; the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, and the Department of Genetics, Harvard Medical School, Boston, MA. The FIP1L1-PDGFRA oncogene is a common cause of chronic eosinophilic leukemia (CEL), and encodes an activated tyrosine kinase that is inhibited by imatinib. FIP1L1-PDGFRA–positive patients with CEL respond to low-dose imatinib therapy, but resistance due to acquired T674I mutation has been observed. We report here the identification of sorafenib as a potent inhibitor of the FIP1 like 1–platelet-derived growth factor receptor alpha (FIP1L1-PDGFR) (T674I) mutant. Sorafenib inhibited the proliferation of FIP1L1-PDGFR and FIP1L1-PDGFR(T674I)–transformed Ba/F3 cells and induced apoptosis of the EOL-1 cell line at a low nanomolar concentration. Western blot analysis confirmed that these effects were due to a direct effect on FIP1L1-PDGFR and FIP1L1-PDGFR(T674I). Sorafenib was recently approved for the treatment of renal cell carcinoma. Our data suggest that low doses of sorafenib could be efficient for the treatment of FIP1L1-PDGFRA–positive CEL and could be used to overcome resistance to imatinib associated with the T674I mutation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. D. Klion How I treat hypereosinophilic syndromes Blood, October 29, 2009; 114(18): 3736 - 3741. [Abstract] [Full Text] [PDF] J. Thiele Philadelphia Chromosome-Negative Chronic Myeloproliferative Disease Am J Clin Pathol, August 1, 2009; 132(2): 261 - 280. [Abstract] [Full Text] [PDF] T. Kurosu, M. Ohki, N. Wu, H. Kagechika, and O. Miura Sorafenib Induces Apoptosis Specifically in Cells Expressing BCR/ABL by Inhibiting Its Kinase Activity to Activate the Intrinsic Mitochondrial Pathway Cancer Res., May 1, 2009; 69(9): 3927 - 3936. [Abstract] [Full Text] [PDF] B. Escudier, C. Szczylik, T. E. Hutson, T. Demkow, M. Staehler, F. Rolland, S. Negrier, N. Laferriere, U. J. Scheuring, D. Cella, et al. Randomized Phase II Trial of First-Line Treatment With Sorafenib Versus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., March 10, 2009; 27(8): 1280 - 1289. [Abstract] [Full Text] [PDF] T. Negri, G. M. Pavan, E. Virdis, A. Greco, M. Fermeglia, M. Sandri, S. Pricl, M. A. Pierotti, S. Pilotti, and E. Tamborini T670X KIT Mutations in Gastrointestinal Stromal Tumors: Making Sense of Missense J Natl Cancer Inst, February 4, 2009; 101(3): 194 - 204. [Abstract] [Full Text] [PDF] L. Jilaveanu, C. Zito, S. J. Lee, K. L. Nathanson, R. L. Camp, D. L. Rimm, K. T. Flaherty, and H. M. Kluger Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib Clin. Cancer Res., February 1, 2009; 15(3): 1076 - 1085. [Abstract] [Full Text] [PDF] L. Dal Lago, V. D'Hondt, and A. 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