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Stem Cells

Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage

Leukemia volume 20, pages 1117–1122 (2006)Cite this article

Abstract

Anagrelide (ANA) and hydroxycarbamide (HC) are two distinct pharmacological agents used to treat thrombocythaemia associated with myeloproliferative disorders. Although both drugs have been in clinical use for a number of years, comparative studies of their selectivity and mode of action are still lacking. Here, we have evaluated the activities of ANA and HC on the growth and differentiation of human haematopoietic progenitor cells in liquid culture. Both drugs inhibited thrombopoietin-induced megakaryocytopoiesis in a dose-dependent manner, but with strikingly different potencies (IC50=26 nM for ANA and 30 μ M for HC) and modes of action. Whereas HC inhibited cell proliferation, ANA acted primarily on the differentiation process. At doses that abrogated megakaryocytopoiesis, HC also inhibited the expansion of CD34+ cells stimulated by stem cell factor, interleukin-3 and Flt-3 ligand and also induced apoptosis. Furthermore, HC inhibited erythroid and myelomonocytic cell growth, induced by erythropoietin or granulocyte–macrophage colony-stimulating factor, respectively. In contrast, ANA showed none of these additional effects. Taken together, these results demonstrate that ANA is a potent and selective inhibitor of megakaryocytopoiesis, having no significant activity against haematopoietic progenitor cell expansion or differentiation into other lineages. In contrast, the anti-megakaryocytopoietic activity of HC cannot be dissociated from its more general cytoreductive and cytotoxic actions.

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Acknowledgements

We thank Dr Richard Franklin and Dr Maggi Moss for their valuable advice during the course of this work.

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Authors and Affiliations

  1. The Wolfson Institute for Biomedical Research, University College London, London, UK

    Y Hong, G Wang, A Gutierrez del Arroyo, J Hernandez, C Skene & J D Erusalimsky

  2. University of Wales Institute, Cardiff, Cardiff School of Health Sciences, Cardiff, UK

    J D Erusalimsky

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  1. Y Hong
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Correspondence to J D Erusalimsky.

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Hong, Y., Wang, G., del Arroyo, A. et al. Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage. Leukemia 20, 1117–1122 (2006). https://doi.org/10.1038/sj.leu.2404180

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