Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/9670
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors |
Author: | Dewar, A. Domaschenz, R. Doherty, K. Hughes, T. Lyons, A. |
Citation: | Leukemia, 2003; 17(9):1713-1721 |
Publisher: | Nature Publishing Group |
Issue Date: | 2003 |
ISSN: | 0887-6924 1476-5551 |
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. |
Keywords: | Eosinophils Neutrophils Monocytes Bone Marrow Cells Hematopoietic Stem Cells Cells, Cultured Macrophages Humans Benzamides Piperazines Pyrimidines Receptor, Macrophage Colony-Stimulating Factor Receptors, Platelet-Derived Growth Factor Macrophage Colony-Stimulating Factor Fusion Proteins, bcr-abl Antineoplastic Agents Antigens, CD34 Enzyme Inhibitors Colony-Forming Units Assay Cell Division Cell Differentiation Cell Lineage Proto-Oncogene Proteins c-kit Protein-Tyrosine Kinases In Vitro Techniques Imatinib Mesylate |
DOI: | 10.1038/sj.leu.2403071 |
Published version: | http://dx.doi.org/10.1038/sj.leu.2403071 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.