白血病干细胞（LSCs）的持续存在可导致白血病的耐药复发，而自我更新能力是LSCs能够持续存在的主要原因之一，因此，针对LSCs自我更新能力的干预有望实现LSCs的彻底清除。既往研究报道DNA损伤反应（DDR）相关基因与干细胞自我更新能力的维持具有一定的相关性。我们前期研究证实：1）基因DBC1通过调控非同源重组（NHEJ）修复途径上相关基因的表达进而参与白血病细胞的DDR；2) DBC1缺失可导致LSCs自我更新能力的明显下降。因此，我们提出科学假说：DBC1通过DDR途径来维持基因组的稳定性进而调控LSCs自我更新能力。本课题拟利用条件敲除DBC1的白血病小鼠模型和AML临床标本在分子、细胞和动物模型等多水平多层次上对DBC1进行功能性研究，探讨DBC1调控LSCs自我更新能力的作用机制，为实现针对LSCs的靶向治疗提供理论基础。

The self-renewal of leukemia stem cells(LSCs) is responsible for their persistence which results in relapsed and chemo-resistant status of leukemia ,so targeting self-renewal is possible to eliminate LSCs. It is reported that several genes that participate in the DNA damage response play a role in the self-renewal of stem cells. Our prior results showed that DBC1 (deleted in breast cancer-1) participated in the DDR of leukemia cells by the means of regulation of the expression of genes related to NHEJ. And Defect of DBC1 impairs the self-renewal of LSCs. So it is hypothesied that DBC1 regulates the self-renewal of LSCs through involving in DDR to maintain the genome. Thus ,we plan to investigate the function of DBC1 in LSCs by the means of various methods in mouse leukemia models and AML clinical samples, in order to explore the mechanism of DBC1 in self-renewal of LSCs.