申请者2011年报道（Plos综合）：IKKβ能调节放疗引起的乳腺癌细胞DNA损伤修复，并且非依赖于Rel A。随后发现特异性IKKβ抑制剂BMS-345541可以抑制放疗引起的DNA损伤的HR（同源重组）修复，显著增敏放疗作用(Clinical Cancer Research审稿中)。放疗与化疗引起DNA损伤的机制虽然不同却有相似修复机制,因此BMS-345541很可能抑制化疗药物引起的DNA损伤修复。慢粒白血病BCR-ABL融合蛋白可刺激CD34+白血病细胞错误修复的DNA累积，导致急变；那么,BMS-345541能否通过抑制化疗药物诱导的DNA损伤修复，清除白血病细胞，尤其是修复能力很强的白血病干细胞，预防慢粒急变和复发？本课题以慢粒白血病细胞及人白血病干细胞为模型，从分子、细胞、动物水平，探讨BMS-345541治疗白血病的优越性及IKKβ调控DNA修复的分子机制。

The applicant reported in 2011 that IKKβ could regulate the repair of DSBs independent of the NF-κB transcriptional activity and inhibition of IKKβ activity can sensitize cancer cells to IR at least in part via inhibition of DSB repair. Based on this finding, we reported that BMS-345541 (a specific IKKβ inhibitor) selectively inhibited homologous recombinational (HR) repair of DNA damage in MCF-7 cells, which sensitizes MCF-7 xenograft tumors to radiation therapy in vivo (Under review by Clinical Cancer Research ). Although there is different mechanism between radiation and chemotherapeutic agents induced DNA damage，they has similar DNA repair mechanism. Thus BMS-345541 is very possile to inhibit DNA repair induced by DNA damaging agents. Moreover, BCR-ABL fusion protein in chronic myeloid leukemia （CML）CD34+ stem/progenitor cells is able to stimulate infidelity DNA repair, resulting in incorrect DNA accumulation followed by CML blast. Based on this finding, our hypothesis is that IKKβ inhibitor BMS-345541 could eradicate leukemia cells, including leukemia stem cell who has strong capability of DNA repair, by blocking DNA damage repair induced by chemotherapeutics. To explore these hypothesis, we plan to use chronic myeloid leukemia cells and leukemia stem cells as model to study in vivo and in vitro the advantage of CML therapy by IKKβ inhibitor BMS-345541，as well as the molecular mechanism by which IKKβ regulate DNA damage repair.