| First Author | Brinkmann K | Year | 2020 |
| Journal | EMBO J | Pages | e105561 |
| PubMed ID | 33236795 | Mgi Jnum | J:300148 |
| Mgi Id | MGI:6491817 | Doi | 10.15252/embj.2020105561 |
| Citation | Brinkmann K, et al. (2020) BCL-XL exerts a protective role against anemia caused by radiation-induced kidney damage. EMBO J :e105561 |
| abstractText | 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 gamma-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. |
