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dc.contributor.authorDebrincat, MA
dc.contributor.authorPleines, I
dc.contributor.authorLebois, M
dc.contributor.authorLane, RM
dc.contributor.authorHolmes, ML
dc.contributor.authorCorbin, J
dc.contributor.authorVandenberg, CJ
dc.contributor.authorAlexander, WS
dc.contributor.authorNg, AP
dc.contributor.authorStrasser, A
dc.contributor.authorBouillet, P
dc.contributor.authorSola-Visner, M
dc.contributor.authorKile, BT
dc.contributor.authorJosefsson, EC
dc.date.accessioned2021-02-05T00:51:49Z
dc.date.available2021-02-05T00:51:49Z
dc.date.issued2015-04-01
dc.identifierpii: cddis201597
dc.identifier.citationDebrincat, M. A., Pleines, I., Lebois, M., Lane, R. M., Holmes, M. L., Corbin, J., Vandenberg, C. J., Alexander, W. S., Ng, A. P., Strasser, A., Bouillet, P., Sola-Visner, M., Kile, B. T. & Josefsson, E. C. (2015). BCL-2 is dispensable for thrombopoiesis and platelet survival. CELL DEATH & DISEASE, 6 (4), https://doi.org/10.1038/cddis.2015.97.
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11343/260182
dc.description.abstractNavitoclax (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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleBCL-2 is dispensable for thrombopoiesis and platelet survival
dc.typeJournal Article
dc.identifier.doi10.1038/cddis.2015.97
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentSchool of BioSciences
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyScience
melbourne.source.titleCell Death and Disease
melbourne.source.volume6
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid971874
melbourne.contributor.authorJosefsson, Emma
melbourne.contributor.authorKile, Benjamin
melbourne.contributor.authorStrasser, Andreas
melbourne.contributor.authorNg, Ashley
melbourne.contributor.authorVandenberg, Cassandra
melbourne.contributor.authorBouillet, Philippe
melbourne.contributor.authorAlexander, Warren
melbourne.contributor.authorDEBRINCAT, MARLYSE ANNE
melbourne.contributor.authorPLEINES, IRINA
dc.identifier.eissn2041-4889
melbourne.identifier.fundernameidNHMRC
melbourne.accessrightsOpen Access


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