Journal article
BCL-2 is dispensable for thrombopoiesis and platelet survival
MA Debrincat, I Pleines, M Lebois, RM Lane, ML Holmes, J Corbin, CJ Vandenberg, WS Alexander, AP Ng, A Strasser, P Bouillet, M Sola-Visner, BT Kile, EC Josefsson
Cell Death and Disease | Published : 2015
Abstract
Navitoclax (ABT-263), an inhibitor of the pro-survival BCL-2 family proteins BCL-2, BCL-XL and BCL-W, has shown clinical efficacy in certain BCL-2-dependent haematological cancers, but causes dose-limiting thrombocytopaenia. The latter effect is caused by Navitoclax directly inducing the apoptotic death of platelets, which are dependent on BCL-XL for survival. Recently, ABT-199, a selective BCL-2 antagonist, was developed. It has shown promising anti-leukaemia activity in patients whilst sparing platelets, suggesting that the megakaryocyte lineage does not require BCL-2. In order to elucidate the role of BCL-2 in megakaryocyte and platelet survival, we generated mice with a lineage-specific ..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
We thank M. Carpinelli, S. Grabow, J. McManus, S. Green, K. Franks, E. Simankowicz, K. Stoev, M. Do and L. Wilkins for outstanding assistance; and J. Zhang, D. Segal and M. Van Delft for methodological advice. This work was supported by Project Grants (575535, 1079250, 1060179), Program Grants (1016647, 1016701), Fellowships (BTK 1063008, WSA 1058344, AS 1020363) and an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council; a fellowship from the Sylvia and Charles Viertel Foundation (BTK); a fellowship from the German Research Foundation (IP DFG, PL707/1-1); the Australian Cancer Research Fund, the Science and Industry Endowment Fund; the Sir Edward Dunlop Medical Research Foundation Grant (APN), the Leukemia and Lymphoma Society Specialized Center of Research Grant (7001-13) and a Victorian State Government Operational Infrastructure Support Grant.