BCL-XL exerts a protective role against anemia caused by radiation-induced kidney damage
- Brinkmann, K; Waring, P; Glaser, SP; Wimmer, V; Cottle, DL; Tham, MS; Nhu, D; Whitehead, L; Delbridge, AR; Lessene, G; Smyth, IM; Herold, MJ; Kelly, GL; Grabow, S; Strasser, A;
Publication Year 2020-11-25, Volume 39, Issue #24, Page e105561
- Journal Title
- Embo J
- Publication Type
- Journal Article
- 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 epithelium with secondary obstructive nephropathy. These findings identify a critical protective role of BCL-XL in the adult kidney and inform on the use of BCL-XL inhibitors in combination with DNA damage-inducing drugs for cancer therapy. Encouragingly, the combination of DNA damage-inducing anti-cancer therapy plus a BCL-XL inhibitor could be tolerated in mice, at least when applied sequentially.
- Bcl-xl; BH3-mimetic drugs; DNA damage; apoptosis; kidney failure
- WEHI Research Division(s)
- Advanced Technology And Biology; Chemical Biology; Blood Cells And Blood Cancer
- PubMed ID
- Publisher's Version
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- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:07:36Last Modified: 2021-03-02 11:07:31