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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2006 Accepted April 10, 2006 Sorafenib (BAY43-9006) 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* Department of Human Genetics-Flanders Interuniversity Institute for Biotechnology (VIB),University Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School Department of Hematology, UZ Leuven, University of Leuven, Leuven, Belgium Department of Human Genetics, University of Leuven, Leuven, Belgium * Corresponding author; email: jan.cools{at}med.kuleuven.be. 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 CEL patients 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 low nanomolar concentration. Western blot analysis confirmed that these effects were due to a direct effect on FIP1L1-PDGFR and FIP1L1-PDGFR (T674I). Sorafenib (BAY43-9006, Nexavar® ) 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? 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