Journal article
MCL-1 but not BCL-XL is critical for the development and sustained expansion of thymic lymphoma in p53-deficient mice
S Grabow, ARD Delbridge, LJ Valente, A Strasser
Blood | Published : 2014
Abstract
Apoptosis plays a role in normal lymphopoiesis and lymphoid malignancies. Pro-survival MCL-1 is essential for survival of T-cell progenitors, BCL-XL for immature thymocytes, and BCL-2 for mature T cells. Conversely, little is known about the regulators that are required for the survival of T-cell lymphomas. We used constitutive and conditionally gene-targeted mice to investigate which pro-survival BCL-2 family memberis required for the sustained survival of thymic lymphomas initiated by loss of p53. Constitutive loss of a single Mcl-1 allele delayed tumor onset. In contrast, lymphomas emerging in p53-/- mice in which Mcl-1 could be conditionally deleted had been selected for retention of MCL..
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Funding Acknowledgements
This work was supported by grants and fellowships from the Cancer Council of Victoria (postdoctoral fellowship to S.G., Sydney Parker Smith postdoctoral research fellowship to A.R.D.D., and postgraduate research scholarship to L.J.V.), the Lady Tata Memorial Trust (postdoctoral research award to S.G.), National Health and Medical Research Council (program grant 1016701; National Health and Medical Research Council fellowship 1020363 (to A.S.), the Leukemia and Lymphoma Society (Specialized Centres of Research grant 7001-03, to A.S.), University of Melbourne International Research Scholarship (to S.G.), University of Melbourne International Fee Remission scholarship (to S.G.), Australian Postgraduate award (to A.R.D.D.), Cancer Therapeutics CRC Top-up scholarship (to S.G. and A.R.D.D.), and the operational infrastructure grants through the Australian Government Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support.