Lady Davis Institute for Medical Research, Cancer Segal Center, Sir M.B. Davis Jewish General Hospital, QC, Canada.
Leuk Res. 2011 Jan;35(1):99-102. doi: 10.1016/j.leukres.2010.05.029. Epub 2010 Jun 22.
B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and there is no cure for the disease. Although dasatinib is cytotoxic to primary CLL lymphocytes in vitro, the drug has been shown to be active in a small percent of CLL patients. Our previous results suggest that dasatinib targets del17 CLL lymphocytes which are the CLL patients with the worst prognosis. Here we present mechanistic evidence that dasatinib induces endoplasmic reticulum stress and autophagy in CLL lymphocytes. Furthermore we provide evidence suggesting that autophagy mediates resistance to the drugs, process that is modulated by p53.
B 细胞慢性淋巴细胞白血病（CLL）是成人中最常见的白血病，目前尚无治愈方法。尽管达沙替尼在体外对原代 CLL 淋巴细胞具有细胞毒性，但该药已被证明对一小部分 CLL 患者有效。我们之前的研究结果表明，达沙替尼靶向 del17 CLL 淋巴细胞，这是预后最差的 CLL 患者。在这里，我们提出了机制证据，表明达沙替尼诱导 CLL 淋巴细胞内质网应激和自噬。此外，我们提供的证据表明，自噬介导对药物的耐药性，该过程受 p53 调节。
