Dual inhibition of the homologous recombinational repair and the nonhomologous end-joining repair pathways in chronic lymphocytic leukemia therapy
Dual inhibition of the homologous recombinational repair and the nonhomologous end-joining repair pathways in chronic lymphocytic leukemia therapy
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DOI：
10.1016/j.leukres.2011.01.004
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发表时间：
2011-08-01
影响因子：
2.7
通讯作者：
Panasci, Lawrence
中科院分区：
文献类型：
--
作者：
Amrein, Lilian;Davidson, David;Panasci, Lawrence
慢性淋巴细胞白血病(CLL)对氯苯丁尼的耐药性与DNA修复增加有关。具体地说，抑制调节RAD51定向同源重组的c-ABL或抑制DNA-PK依赖的非同源末端连接都能使原代CLL淋巴细胞对氯氨丁苯敏感。在这里，我们报道抑制c-ABL可以导致DNA-PK的代偿性增加，从而抑制c-ABL和DNA-PK最佳地使CLL淋巴细胞对氯氨丁苯敏感。在这篇文章中，我们报道了药物诱导的两条DNA修复途径之间的代偿性改变，在CLL治疗中具有潜在的治疗意义。(C)2011爱思唯尔有限公司。保留所有权利。
Resistance to chlorambucil in chronic lymphocytic leukemia (CLL) has been associated with increased DNA repair. Specifically, inhibition of either c-abl, which modulates Rad51 directed homologous recombination or DNA-PK dependent nonhomologous end joining has been shown to sensitize primary CLL lymphocytes to chlorambucil. Here we report that inhibition of c-abl can result in a compensatory increase in DNA-PK and thus inhibition of both c-abl and DNA-PK optimally sensitizes CLL lymphocytes to chlorambucil. In this paper we report a drug-induced compensatory change between two DNA repair pathways with potential therapeutic implications in CLL therapy. (C) 2011 Elsevier Ltd. All rights reserved.