Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors
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Updated: Sep 20, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
A L Dewar1, R M Domaschenz, K V Doherty
1Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
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.
Insights
Imatinib, an anti-cancer drug, inhibits monocyte and macrophage development from bone marrow progenitors at low concentrations. This finding suggests potential therapeutic applications for imatinib in diseases involving these cells.
Area of Science:
- Hematology
- Pharmacology
- Cell Biology
Background:
- Imatinib is a tyrosine kinase inhibitor targeting BCR-ABL in CML.
- Its effects on other kinases like c-ABL, PDGFR, and c-KIT are known.
- The impact of imatinib on normal hematopoietic progenitor differentiation requires further investigation.
Purpose of the Study:
- To investigate the effect of imatinib on in vitro differentiation of normal bone marrow progenitors.
- To determine the specific impact on monocyte/macrophage lineage development.
- To explore the potential therapeutic implications of imatinib's effects on myeloid development.
Main Methods:
- In vitro culture of normal bone marrow progenitors in semisolid agar and liquid media.
- Treatment with varying concentrations of imatinib (0.1-5.0 microM).
- Assessment of monocyte, macrophage, neutrophil, and eosinophil development and maturation.
Main Results:
- Imatinib significantly inhibited in vitro monocyte/macrophage development at concentrations as low as 0.3 microM.
- Neutrophil and eosinophil development were less affected.
- Imatinib impaired monocyte maturation into macrophages at 1.0 microM.
- Inhibition occurred irrespective of M-CSF stimulation, suggesting c-FMS inhibition is not the primary mechanism.
Conclusions:
- Imatinib inhibits normal monocyte/macrophage development at pharmacologically achievable concentrations.
- The mechanism may involve inhibition of kinases other than c-FMS crucial for myeloid differentiation.
- Imatinib or related compounds show potential for treating diseases where monocytes/macrophages play a pathogenic role.
