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Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib

Citation

Dewar, AL and Cambareri, AC and Zannettino, ACW and Doherty, KV and Hughes, TP and Lyons, AB, Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib, Blood, 105, (8) pp. 3127-3132. ISSN 0006-4971 (2005) [Refereed Article]


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Copyright Statement

Copyright 2005 The American Society of Hematology

DOI: doi:10.1182/blood-2004-10-3967

Abstract

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Lyons, AB (Dr Bruce Lyons)
ID Code:73621
Year Published:2005
Web of Science® Times Cited:202
Deposited By:Medicine (Discipline)
Deposited On:2011-10-19
Last Modified:2012-06-26
Downloads:0

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