Journal article

BCL-XL exerts a protective role against anemia caused by radiation-induced kidney damage

Kerstin Brinkmann, Paul Waring, Stefan P Glaser, Verena Wimmer, Denny L Cottle, Ming Shen Tham, Duong Nhu, Lachlan Whitehead, Alex RD Delbridge, Guillaume Lessene, Ian M Smyth, Marco J Herold, Gemma L Kelly, Stephanie Grabow, Andreas Strasser

The EMBO Journal | WILEY | Published : 2020

Abstract

Studies of gene-targeted mice identified the roles of the different pro-survival BCL-2 proteins during embryogenesis. However, little is known about the role(s) of these proteins in adults in response to cytotoxic stresses, such as treatment with anti-cancer agents. We investigated the role of BCL-XL in adult mice using a strategy where prior bone marrow transplantation allowed for loss of BCL-XL exclusively in non-hematopoietic tissues to prevent anemia caused by BCL-XL deficiency in erythroid cells. Unexpectedly, the combination of total body γ-irradiation (TBI) and genetic loss of Bcl-x caused secondary anemia resulting from chronic renal failure due to apoptosis of renal tubular epitheli..

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Grants

Awarded by National Health and Medical Research Council


Awarded by NHMRC Australia


Awarded by Leukemia and Lymphoma Society (SCOR)


Funding Acknowledgements

We thank Drs P Bouillet, JM Adams, L Hennighausen and A Villunger for gifts of mice; T. Kitson, C D'Alessandro, 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. We thank Dr LA O'Reilly for helping with the TUNEL assays. We thank Dr KA Sarosiek for helpful discussions of some results. This work was supported by grants and fellowships from the Deutsche Krebshilfe (Dr Mildred Scheel post-doctoral fellowship to KB), Cancer Council of Victoria (SG, AD "Sydney Parker Smith Postdoctoral Fellowship"), Leukaemia Foundation Australia (SG), the Lady Tata Memorial Trust (SG), Cure Brain Cancer Australia (AS), the National Health and Medical Research Council (Program Grants #1016701 and 1016647, NHMRC Australia Fellowship 1020363; all to AS), (Project Grants 1145728 to MJH, 1143105 to MJH and AS, and Fellowships 1156095 to MJH) the Leukemia and Lymphoma Society (SCOR Grant #7001-03 to AS), 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.