急性髓系白血病（acute myeloid leukemia，AML）是髓系原始细胞分化障碍导致的恶性疾病。由t(8;21)染色体易位产生的融合蛋白AML1-ETO所引起的转录失调是导致t(8;21)AML的重要病因。目前AML细胞分化阻滞的机制尚不明确，同时缺乏有效的靶向治疗药物，患者五年总体生存率低于30%。我们前期发现CEBPE-S100A8/A9是AML1-ETO的潜在作用靶点。在此基础上，我们推测AML1-ETO可能通过抑制CEBPE-S100A8/A9通路，阻滞了髓系原始细胞分化，从而促进了AML发生。为验证该假设，本课题拟通过分子生物学和细胞生物学的方法，在细胞、动物以及临床样本中解析AML1-ETO-CEBPE-S100A8/A9参与调控t(8;21)AML细胞定向分化的功能和分子机理，并对其可能的治疗作用做初步探讨。本项目的顺利完成将为该病的治疗提供新思路。

Acute myeloid leukemia (AML) is characterized by a differentiation block in the myeloid lineages of the hematopoiesis. AML1-ETO, a t(8;21) fusion protein, is the major molecular player leading to t(8;21) AML. The AML1-ETO fusion protein initiates AML by blocking the differentiation and increasing self-renewal of leukaemic progenitor cells. The five-year survival rate of t(8;21) AML is less than 30%. There is currently no effective therapy for t(8;21) AML patients mostly due to the lack of understanding the molecular mechanism related to differentiation and maturation of AML1-ETO positive AML cells. Based on our previous data, we hypothesize that CEBPE and its targets S100A8/A9 could mediate AML1-ETO function in the differentiation and mature of AML cells. In this study, we will further validate this hypothesis in AML cells both from transgenic mouse and AML patients by using the advanced cellular and molecular techniques. The accomplishment of this study would provide a possibility to develop new therapeutic strategies for curing t(8;21) AML patients.