慢性淋巴细胞白血病（CLL）是B细胞克隆性增殖疾病中最常见的一类。Bcl-2的高表达是维持其抗凋亡并持续积累的重要因素，然而调控Bcl-2信号通路参与CLL发病的分子机制目前尚不清楚。COP1是调控p53泛素化降解、参与肿瘤细胞增殖与凋亡进程的泛素连接酶，但迄今，COP1在CLL发病中的作用未见报道。我们研究显示，在CLL细胞中，Bcl-2的表达受p53—Brn-3a复合物的调节。进一步发现，COP1在CLL病例中高表达，并通过抑制CLL细胞系中p53—Brn-3a复合物的形成促进Bcl-2表达，提示COP1可能参与CLL的发病过程。本研究拟进一步结合CLL临床病例，体外及动物实验，阐明COP1通过p53—Brn-3a复合物调控Bcl-2表达在CLL发病中的分子机制。如期完成后，可加深对CLL发病机制的认识。

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia characterized by clonal B-cell proliferation. A key feature of CLL cells is the high expression level of the anti-apoptotic protein Bcl-2, which maintains apoptotic resistance and confers a consistent-accumulation phenotype. However, the pathogenesy was unclear in the development of CLL via regulation of Bcl-2 pathway. COP1, an E3 ubiquitinligase, has been reported to be involved in proliferation and apoptosis in cancer cells through regulating the ubiquitin degradation of p53. As yet, the effect of COP1 in CLL has not been reported. Our previous study showed that the expression of Bcl-2 was regulated by p53-Brn-3a complex in CLL cells. In addition, high expression level of COP1 in CLL sample and cell line inhibited the formation of p53-Brn-3a complex, which further promoted the expression of Bcl-2, suggesting the involvement of COP1 in the pathogenesy of CLL. The purpose of this project is to elucidate how the COP1 regulated the expression of Bcl-2 through p53-Brn-3a complex, involving the pathogenesy of CLL. This study would improve the understanding of CLL pathogenesy.