CEBPA基因突变是急性髓系白血病（AML）最常见的基因突变之一。CEBPA基因编码的C/EBPα蛋白是重要的髓系分化转录因子，并有抑癌蛋白功能。我们前期研究发现，C/EBPα蛋白N'端TAD1结构域突变体及C’端bZIP结构域突变体失去诱导AML细胞凋亡及抑制AML细胞增殖的功能。进一步研究发现两种突变体与P53结合能力明显减弱或缺失，而N’端TAD2结构域突变体则保留了P53结合能力，同时保留了诱导AML细胞凋亡的功能。由此我们提出C/EBPα与P53结合，稳定并激活P53通路是C/EBPα诱导AML细胞凋亡、抑制细胞增殖的关键环节， P53通路失活极有可能是CEBPA基因突变致AML发生发展的新机制。本项目拟从体内外水平证实C/EBPα通过与P53相互作用发挥肿瘤监视功能，阐明P53通路失活在CEBPA基因突变致AML发生发展中的作用和机制，为AML的防治提供理论依据。

CEBPA mutations is one kind of the most common mutations in patients with normal karyotype acute myeloid leukemia (AML). CCAAT enhancer-binding protein ( C/EBPα) is a key transcript factors in myelogenesis and acts as a tumor suppressor protein. In our study we found that C/EBPα with mutation in TAD1 domain or bZIP domain lost their function of inducing apoptosis and arresting cell growth in AML cells. In further study we found that P53 binding ability was altered in C/EBPα mutant compared with wild type. Moreover, C/EBPα with mutation in TAD2 domain retained their P53 affinity and apoptosis inducing function. Here we suggest that the binding of C/EBPα and P53 is vital in surveillance of AML . Impaired P53 binding abilities of C/EBPα mutants lead to excessive proliferation, differentiation failure and apoptosis disorder of transformed cells, and finally lead to the occurrence and development of AML. Our research intends to demonstrate the role of C/EBPα-P53 complex in surveillance of AML , and to reveal the molecular mechanisms of AML development caused by CEBPA mutations. Our study aims to provide new clues to the prevention and treatment of AML.