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Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors

Citation

Dewar, AL and Domaschenz, RM and Doherty, KV and Hughes, TP and Lyons, AB, Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors, Leukemia, 17, (9) pp. 1713-1721. ISSN 0887-6924 (2003) [Refereed Article]

Copyright Statement

Copyright 2003 Nature Publishing Group

DOI: doi:10.1038/sj.leu.2403071

Abstract

The antileukaemic tyrosine kinase inhibitor, imatinib, has been reported to inhibit specifically the growth of bcr-abl expressing CML progenitors at levels of 0.1-5.0 microM, by blocking the ATP-binding site of the kinase domain of bcr-abl. Inhibition of the c-abl, platelet-derived growth factor receptor and stem cell factor receptor (c-kit) tyrosine kinases by imatinib has also been reported. Here, we demonstrate that imatinib significantly inhibits in vitro monocyte/macrophage development from normal bone marrow progenitors, while neutrophil and eosinophil development was less affected. Monocyte/macrophage inhibition was observed in semisolid agar and liquid cultures at concentrations of imatinib as low as 0.3 microM. The maturation of monocytes into macrophages was also found to be impaired following treatment of cultures with 1.0 microM imatinib. Imatinib blocked monocyte/macrophage development in cultures stimulated with and without M-CSF, suggesting that inhibition of the M-CSF receptor, c-fms, by imatinib was unlikely to be responsible. Imatinib may therefore have an inhibitory activity for other kinase(s) that play a role in monocyte/macrophage differentiation. This inhibition of normal monocyte/macrophage development was observed at concentrations of imatinib achievable pharmacologically, suggesting that imatinib or closely related derivatives may have potential for the treatment of diseases where monocytes/macrophages contribute to pathogenesis.

Item Details

Item Type:Refereed Article
Keywords:tyrosine kinase inhibitor, bone marrow progenitors
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:Blood Disorders
Author:Doherty, KV (Dr Kathleen Doherty)
Author:Lyons, AB (Dr Bruce Lyons)
ID Code:127630
Year Published:2003
Web of Science® Times Cited:46
Deposited By:Medicine (Discipline)
Deposited On:2018-08-07
Last Modified:2018-09-19
Downloads:0

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