p53 and autophagy contribute to dasatinib resistance in primary CLL lymphocytes

被引：41

作者：

Amrein, Lilian ^{[1
]}

Soulieres, Denis ^{[2
,3
]}

Johnston, James B. ^{[4
]}

Aloyz, Raquel ^{[1
]}

机构：

[1] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Canc Segal Ctr, Montreal, PQ H3T 1E2, Canada

[2] Univ Montreal, Dept Med, Serv Hematol & Med Oncol, Ctr Hosp, Montreal, PQ H3C 3J7, Canada

[3] Ctr Rech CHUM, Montreal, PQ, Canada

[4] Canc Care Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada

来源：

LEUKEMIA RESEARCH | 2011年 / 35卷 / 01期

关键词：

CLL; Dasatinib; p53; Autophagy; LEUKEMIA LYMPHOCYTES; IN-VITRO; CELLS;

D O I：

10.1016/j.leukres.2010.05.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 dell 7 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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：99 / 102

页数：4

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