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Second-generation TKI dasatinib inhibits proliferation of mesenchymal stem cells and osteoblast differentiation in vitro

Leukemia volume 24, pages 1357–1359 (2010)Cite this article

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Patients with chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor (TKI) imatinib have increased bone mineral density (BMD).1, 2, 3 Considering that dasatinib and imatinib partly inhibit the same tyrosine kinases, similar effects on bone metabolism might be seen with the second-generation TKI dasatinib.

The skeleton is continuously remodeled throughout life and to maintain bone homeostasis the activity of bone-forming osteoblasts and bone-resorbing osteoclasts is tightly coupled. The increased BMD observed in imatinib-treated patients1, 2, 3 can thus be due to diminished bone degradation or increased bone formation. Imatinib inhibits differentiation and activity of osteoclasts in vitro and in animals through the inhibition of colony-stimulating factor 1 receptor (CSF1R), and dasatinib seems to have similar effects on osteoclasts.4, 5, 6, 7 The effects of imatinib on osteoblast differentiation are, however, less uniform.7, 8 Whether the second-generation TKI dasatinib influences osteoblast proliferation and differentiation in vitro has not previously been reported.

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Acknowledgements

This work was supported by grants from the Norwegian Cancer Society, the Norwegian Research Council, the Swedish Research Council (529-2004-6512 and 521-2006-5103), the Swedish federal government under the LUA/ALF agreement, the Sahlgrenska University Hospital Foundation and the agreement concerning research and education of doctors in Västra Götaland, Sweden. We thank BMS for supplying dasatinib. We also thank Berit Størdal and Hanne Hella (Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology) for technical assistance. HHH has been an investigator in studies sponsored by Novartis and Bristol-Myers Squibb and is a national coordinator in the Nordic CML Study Group that has received economical support from both companies for investigator-initiated trials. HW has been an investigator in studies sponsored by Novartis and Bristol-Myers Squibb and has received unrestricted research grants from Novartis.

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  1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    S Jönsson, H Hjorth-Hansen, A Sundan & T Standal

  2. Department of Internal Medicine, Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden

    S Jönsson, B Olsson & H Wadenvik

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  1. S Jönsson
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Correspondence to T Standal.

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Jönsson, S., Hjorth-Hansen, H., Olsson, B. et al. Second-generation TKI dasatinib inhibits proliferation of mesenchymal stem cells and osteoblast differentiation in vitro. Leukemia 24, 1357–1359 (2010). https://doi.org/10.1038/leu.2010.84

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