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Imatinib mesylate causes growth plate closure in vivo

Leukemia volume 23, pages 2155–2159 (2009)Cite this article

Imatinib mesylate (Glivec/Gleevec, STI571; Novartis, Basel, Switzerland) is a 2-phenylaminopyrimidine-based ATP-competitive protein tyrosine kinase inhibitor, which at pharmacologically-achievable concentrations inhibits the activity of BCR–Abl,1 stem cell factor receptor (c-Kit),2 platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β1 and the macrophage colony-stimulating factor receptor, c-fms (CSF-1R).3 Imatinib is a highly effective treatment for Philadelphia chromosome-positive chronic myeloid leukaemia (CML) and gastro-intestinal stromal tumours, based on the inhibition of BCR–Abl and c-Kit, respectively. Although imatinib is the gold standard therapy for CML in adults, it is only approved for use in paediatric CML cases in which disease recurrence is evident after allogeneic stem cell transplantation, or when paediatric patients show resistance or intolerance to interferon-α therapy. Increasingly, imatinib is used as a front-line therapy in newly diagnosed paediatric CML patients for whom HLA-identical donors are not available.

CML is rarely seen in children and accounts for less than 3% of childhood leukaemias.4 Given this low incidence, it has not been feasible to conduct large-scale phase III trials to determine the long-term effects of imatinib therapy in the paediatric setting. However, although short-term imatinib therapy has been successful and well tolerated in children, there is emerging information suggesting that long-term therapy may have the potential to result in side effects that are specific to the paediatric setting.

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Acknowledgements

We thank Elisabeth Buchdunger, Sonia Yip and Paul Manley from Novartis for their helpful discussions. This research was supported by funding from Novartis and by a grant from the Leukemia and Lymphoma Society Translational Research Program.

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Authors and Affiliations

  1. Division of Haematology, Myeloma Research Program, Bone and Cancer Research Laboratories, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia

    K Vandyke, A L Dewar, S Fitter & A C W Zannettino

  2. Faculty of Health Sciences, University of Adelaide, Adelaide, Australia

    K Vandyke, D Menicanin & A C W Zannettino

  3. Division of Haematology, Mesenchymal Stem Cell Group, Bone and Cancer Research Laboratories, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia

    D Menicanin

  4. Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia

    L B To & T P Hughes

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  1. K Vandyke
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  7. A C W Zannettino
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Correspondence to A C W Zannettino.

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Vandyke, K., Dewar, A., Fitter, S. et al. Imatinib mesylate causes growth plate closure in vivo. Leukemia 23, 2155–2159 (2009). https://doi.org/10.1038/leu.2009.150

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