Department of Oncology, Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada.
Leuk Res. 2011 Aug;35(8):1080-6. doi: 10.1016/j.leukres.2011.01.004. Epub 2011 Feb 1.
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.
慢性淋巴细胞白血病 (CLL) 对苯丁酸氮芥的耐药性与增加的 DNA 修复有关。具体而言，抑制调节 Rad51 指导的同源重组或 DNA-PK 依赖性非同源末端连接的 c-abl 已被证明可使原发性 CLL 淋巴细胞对苯丁酸氮芥敏感。在这里，我们报告抑制 c-abl 可导致 DNA-PK 的代偿性增加，从而抑制 c-abl 和 DNA-PK 可使 CLL 淋巴细胞对苯丁酸氮芥最敏感。在本文中，我们报告了两种 DNA 修复途径之间的药物诱导的代偿性变化，这在 CLL 治疗中具有潜在的治疗意义。
