| First Author | Li YJ | Year | 2017 |
| Journal | Leukemia | Volume | 31 |
| Issue | 9 | Pages | 1905-1914 |
| PubMed ID | 28050012 | Mgi Jnum | J:245803 |
| Mgi Id | MGI:5916679 | Doi | 10.1038/leu.2016.395 |
| Citation | Li YJ, et al. (2017) PPAR-delta promotes survival of chronic lymphocytic leukemia cells in energetically unfavorable conditions. Leukemia 31(9):1905-1914 |
| abstractText | Targeting the mechanisms that allow chronic lymphocytic leukemia (CLL) cells to survive in harsh cancer microenvironments should improve patient outcomes. The nuclear receptor peroxisome proliferator activated receptor delta (PPARdelta) sustains other cancers, and in silico analysis showed higher PPARD expression in CLL cells than normal lymphocytes and other hematologic cancers. A direct association was found between PPARdelta protein levels in CLL cells and clinical score. Transgenic expression of PPARdelta increased the growth and survival of CD5+ Daudi cells and primary CLL cells in stressful conditions including exhausted tissue culture media, low extracellular glucose, hypoxia and exposure to cytotoxic drugs. Glucocorticoids and synthetic PPARdelta agonists up-regulated PPARD expression and also protected Daudi and primary CLL cells from metabolic stressors. Survival in low glucose was related to increased antioxidant expression, substrate utilization and mitochondrial performance, and was reversed by genetic deletion and synthetic PPARdelta antagonists. These findings suggest PPARdelta conditions CLL cells to survive in harsh microenvironmental conditions by reducing oxidative stress and increasing metabolic efficiency. Targeting PPARdelta may be beneficial in the treatment of CLL. |
