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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 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 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 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. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib Andrea L. Dewar, Antony C. Cambareri, Andrew C. W. Zannettino, Bernadette L. Miller, Kathleen V. Doherty, Timothy P. Hughes, and A. Bruce Lyons From the Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science; and the Australian Red Cross Blood Service, Adelaide, South Australia, Australia. Imatinib is a tyrosine kinase inhibitor that suppresses the growth of bcr-abl–expressing chronic myeloid leukemia (CML) progenitor cells by blockade of the adenosine triphosphate (ATP)–binding site of the kinase domain of bcr-abl. Imatinib also inhibits the c-abl, platelet-derived growth factor (PDGF) receptor, abl-related gene (ARG) and stem-cell factor (SCF) receptor tyrosine kinases, and has been used clinically to inhibit the growth of malignant cells in patients with CML and gastrointestinal stromal tumors (GISTs). Although initially considered to have minimal effects of normal hematopoiesis, recent studies show that imatinib also inhibits the growth of some nonmalignant 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 macrophage colony-stimulating factor (M-CSF) receptor c-fms. Phosphorylation of c-fms was inhibited by therapeutic concentrations of imatinib, and this was not due to down-regulation 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 and/or macrophages through inhibition of c-fms signaling. Importantly, these results identify an additional biologic 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. Louvet, G. L. Szot, J. Lang, M. R. Lee, N. Martinier, G. Bollag, S. Zhu, A. Weiss, and J. A. Bluestone Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice PNAS, December 2, 2008; 105(48): 18895 - 18900. [Abstract] [Full Text] [PDF] S. Jonsson, B. Olsson, C. Ohlsson, M. Lorentzon, D. Mellstrom, and H. 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