Journal article

The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL

Alex RD Delbridge, Brandon J Aubrey, Craig Hyland, Jonathan P Bernardini, Ladina Di Rago, Jean-Marc Garnier, Guillaume Lessene, Andreas Strasser, Warren S Alexander, Stephanie Grabow



Anaemia is a major global health problem arising from diverse causes and for which improved therapeutic strategies are needed. Erythroid cells can undergo apoptotic cell death and loss of pro-survival BCL-XL is known to trigger apoptosis during late-stage erythroid development. However, the mechanism by which loss or pharmacological blockade of BCL-XL leads to erythroid cell apoptosis remains unclear. Here we sought to identify the precise stage of erythropoiesis that depends on BCL-XL. We also tested whether deficiency of BIM or PUMA, the two main pro-apoptotic antagonists of BCL-XL, could prevent reticulocyte death and anaemia caused by BCL-XL loss. Using an in vivo mouse model of tamoxife..

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Awarded by National Health and Medical Research Council (NHMRC Australia Fellowship)

Awarded by Leukemia and Lymphoma Society (SOCR Grant)

Awarded by National Health and Medical Research Council (Research Fellowship)

Funding Acknowledgements

We thank Drs P Bouillet, JM Adams, L Hennighausen, and A Villunger for gifts of mice; C Gatt, S O'Connor, J Mansheim, K McKenzie and G Siciliano for expert animal care; B Helbert for genotyping; J Corbin and J McManus for automated blood analysis. This work was supported by grants and fellowships from the Cancer Council of Victoria (SG, AD 'Sydney Parker Smith Postdoctoral Fellowship'), Leukaemia Foundation Australia (SG, BJA), the Lady Tata Memorial Trust (SG), Cure Brain Cancer Australia (AS), the National Health and Medical Research Council (Programme Grants #1016701 and 1016647, NHMRC Australia Fellowship 1020363 to AS and Research Fellowship 1058344 to WSA), the Leukemia and Lymphoma Society (SOCR Grant #7001-03 to AS), The Australian Cancer Research Fund (GL, JG), Melbourne International Research and the Melbourne International Fee Remission Scholarship (University of Melbourne, SG) and Cancer Therapeutics CRC Top-up Scholarship (SG, AD). The estate of Anthony (Toni) Redstone OAM, University of Melbourne International Research and International Fee Remission Scholarships (SG), Australian Postgraduate Award (ARDD, JPB), and the operational infrastructure grants through the Australian Government IRIISS and the Victorian State Government OIS.