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Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis

Leukemia volume 22, pages 649–652 (2008)Cite this article

Nilotinib is a new phenylaminopyrimidine with enhanced activity and selectivity against the Bcr-Abl tyrosine kinase compared with imatinib, and promises to improve upon the treatment of chronic myeloid leukaemia and imatinib-resistant disease.1, 2 Imatinib is well-tolerated by most chronic myeloid leukaemia patients, with a 5-year overall survival rate in newly diagnosed disease of 89%, although it has been observed that some patients showed an association with altered bone and mineral metabolism.3 This effect is suggested to be caused by a reduction in osteoclast activity, perhaps due to the inhibition of platelet derived growth factor (PDGF) or receptor for MCSF (FMS) receptors by imatinib.3

The oncogenic V-Fms receptor is not resistant to imatinib, and Figures 1b and c show that the transformed morphology that is characteristic of rodent fibroblasts that express V-Fms4, 5 is suppressed by nilotinib. Phalloidin staining of actin (Figures 1d and e) shows that nilotinib suppressed membrane ruffling.

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Figure 1
Figure 2

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Acknowledgements

We thank Jan Domin for advice and Stephen Marley, Myrtle Gordon, Ming Hu and Tasios Karadimitris for help with the osteoclast assays. We are also grateful to Malcolm Parker, Robert Winston and the IOG Trust for consumable contributions. NB and AR are recipients of BBSRC studentships.

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Authors and Affiliations

  1. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK

    N Brownlow, A E Russell, H Saravanapavan & N J Dibb

  2. Novartis Institutes for BioMedical Research, Oncology, Novartis Pharma AG, Basel, Switzerland

    M Wiesmann, J M Murray & P W Manley

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  1. N Brownlow
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  2. A E Russell
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Correspondence to N J Dibb.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Brownlow, N., Russell, A., Saravanapavan, H. et al. Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis. Leukemia 22, 649–652 (2008). https://doi.org/10.1038/sj.leu.2404944

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