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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3127-3132. Prepublished online as a Blood First Edition Paper on January 6, 2005; DOI 10.1182/blood-2004-10-3967. This Article Full Text (PDF) All Versions of this Article: 2004-10-3967v1 105/8/3127    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 Dewar, A. L Articles by Lyons, A B Search for Related Content PubMed PubMed Citation Articles by Dewar, A. L Articles by Lyons, A B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 14, 2004 Accepted December 26, 2004 Macrophage colony stimulating factor receptor, c-fms, is a novel target of imatinib Andrea L Dewar*, Antony C Cambareri, Andrew C Zannettino, Bernadette L Miller, Kathleen V Doherty, Timothy P Hughes, and A B Lyons Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia Australian Red Cross Blood Service, Adelaide, SA, Australia * Corresponding author; email: andrea.dewar{at}imvs.sa.gov.au. Imatinib is a tyrosine kinase inhibitor that suppresses the growth of bcr-abl expressing CML progenitor cells by blockade of the ATP-binding site of the kinase domain of bcr-abl. Imatinib also inhibits the c-abl, PDGF receptor, ARG and SCF receptor tyrosine kinases and has been used clinically to inhibit the growth of malignant cells in CML and GIST patients. Although initially considered to have minimal effects of normal hematopoiesis, recent studies show that imatinib also inhibits the growth of some non-malignant hematopoietic cells including monocyte/macrophages. This inhibition could not be attributed to the known activity profile of imatinib. Here, we demonstrate for the first time that imatinib targets the M-CSF receptor, c-fms. Phosphorylation of c-fms was inhibited by therapeutic concentrations of imatinib, and this was not due to downregulation in c-fms expression. Imatinib was also found to inhibit M-CSF-induced proliferation of a cytokine dependent cell line, further supporting the hypothesis that imatinib affects the growth and development of monocyte/macrophages through inhibition of c-fms signalling. Importantly, these results identify an additional biological target to those already defined for imatinib. Imatinib should now be assessed for activity in diseases where c-fms activation is implicated, including breast and ovarian cancer and inflammatory conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Gebhardt, M. Averbeck, U. Paasch, S. Ugurel, H. Kurzen, P. Stumpp, J. C. Simon, and R. Treudler A Case of Cutaneous Rosai-Dorfman Disease Refractory to Imatinib Therapy Arch Dermatol, May 1, 2009; 145(5): 571 - 574. [Abstract] [Full Text] [PDF] K. M. Irvine, M. R. Andrews, M. A. Fernandez-Rojo, K. Schroder, C. J. Burns, S. Su, A. F. Wilks, R. G. Parton, D. A. Hume, and M. J. Sweet Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages J. Leukoc. Biol., February 1, 2009; 85(2): 278 - 288. [Abstract] [Full Text] [PDF] C. Louvet, G. L. Szot, J. Lang, M. R. Lee, N. Martinier, G. Bollag, S. Zhu, A. Weiss, and J. A. 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