Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/123606
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Type: Journal article
Title: BCL-2 is dispensable for thrombopoiesis and platelet survival
Author: Debrincat, M.
Pleines, I.
Lebois, M.
Lane, R.
Holmes, M.
Corbin, J.
Vandenberg, C.
Alexander, W.
Ng, A.
Strasser, A.
Bouillet, P.
Sola-Visner, M.
Kile, B.
Josefsson, E.
Citation: Cell Death and Disease, 2015; 6(4):e1721-1-e1721-8
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 2041-4889
2041-4889
Statement of
Responsibility: 
M A Debrincat, I Pleines, M Lebois, R M Lane, M L Holmes ... B T Kile ... et al.
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 deletion of Bcl2, alone or in combination with loss of Mcl1 or Bclx. Platelet production and platelet survival were analysed. Additionally, we made use of BH3 mimetics that selectively inhibit BCL-2 or BCL-XL. We show that the deletion of BCL-2, on its own or in concert with MCL-1, does not affect platelet production or platelet lifespan. Thrombocytopaenia in Bclx-deficient mice was not affected by additional genetic loss or pharmacological inhibition of BCL-2. Thus, BCL-2 is dispensable for thrombopoiesis and platelet survival in mice.
Keywords: Blood Platelets; Animals; Mice, Transgenic; Mice; Thrombocytopenia; Proto-Oncogene Proteins c-bcl-2; Thrombopoiesis; Cell Survival; bcl-X Protein
Rights: © 2015 Macmillan Publishers Limited All rights reserved
RMID: 1000001833
DOI: 10.1038/cddis.2015.97
Grant ID: http://purl.org/au-research/grants/nhmrc/575535
http://purl.org/au-research/grants/nhmrc/1079250
http://purl.org/au-research/grants/nhmrc/1060179
http://purl.org/au-research/grants/nhmrc/1016647
http://purl.org/au-research/grants/nhmrc/1016701
http://purl.org/au-research/grants/nhmrc/1063008
http://purl.org/au-research/grants/nhmrc/1058344
http://purl.org/au-research/grants/nhmrc/1020363
http://purl.org/au-research/grants/nhmrc/361646
Appears in Collections:Medicine publications

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