MLL白血病是一类化疗效果差和预后不良的血液系统恶性肿瘤，独特的DNA损伤反应在其发生发展中发挥着重要作用，但其机制仍不清。DBC1作为一种核蛋白，参与多种生理过程，尤其在细胞的DNA损伤反应中发挥着重要作用。我们前期研究证实：1）DBC1在白血病细胞中的表达较正常细胞升高，尤其在MLL白血病细胞中升高更为明显；2）下调DBC1的表达减弱了MLL白血病细胞的DNA损伤修复能力，导致细胞周期阻滞和凋亡增加，这提示DBC1表达程度与MLL白血病的DNA损伤反应密切相关，可成为研究的靶点。本课题拟利用各种实验技术在分子、细胞、到白血病动物模型等多水平多层次上对DBC1进行功能性研究，探讨DBC1在MLL白血病细胞的DNA损伤反应中的作用，为改善MLL白血病的预后提供理论基础。

Leukemias with MLL translocations are recognized as having a poor prognosis due to their chemotherapy resistance and characterized by their specific DNA Damage Reponse (DDR) mechanism. However,this mechanism has still been poorly understood so far. DBC1 (deleted in breast cancer-1) is a nuclear protein that involved in several physical process ,especially DDR. Our prior results showed that expression of DBC1 was elevated in leukemia cells when compared to their healthy counterparts , while reduced when compared to MLL leukemia cells. Furthermore , knockdown of DBCl seemed to reduce the capability of DNA repair, leading to cell cycle arrest and apoptosis in leukemia cells. Therefore,this indicated that DBC1 may be associated with MLL leukemia specific DNA damage response mechanisms. Thus, we plan to investigate the function of DBC1 in MLL leukemia cells by the means of various methods at levels of whole animal, cell and molecular models, in order to explore the effect of DBC1 in DNA damage response in MLL leukmia cells.