急性淋巴细胞白血病（ALL）是儿童及年轻成人主要致死的癌症。ALL异质性强，约85%的ALL患者中存在着异常遗传学事件。本研究前期通过对203例ALL基因组学测序发现了包括ZNF384融在内的三类新的融合基因分类。该类型融合基因具有相对独特的免疫学及表达谱特征，已被学者建议纳入到ALL新临床分类亚型中。前期针对融合基因EP300-ZNF384初步研究提示其可影响B细胞分化，并可在转基因小鼠模型中引起白血病发生，提示这一融合突变与特定类型ALL的发生密切相关，但相关机制仍不清楚。本项目聚焦EP300-ZNF384在ALL中的功能，拟基于体外及小鼠白血病模型开展系列研究，进一步深入探讨EP300-ZNF384导致细胞表型的变化及其背后信号通路的调控方式，揭示其参与白血病发生发展的分子机制。预期研究结果不仅会加强我们对于ALL发生病理机制的认识，也有望为ALL的分级分层诊治提供有价值的靶点。

Acute lymphoblastic leukemia (ALL) is the leading cause of death in children and young adults. ALL is a highly heterogeneous malignant disease, and about 85% of ALL patients have recurrent genetic abnormalities. Three new classifications of fusion genes including ZNF384 fusion were discovered by genomic sequencing of 203 ALL cases. This type of fusion gene has relatively unique immunological phenotype and expression profile, and has been proposed to be included in the new clinical classification subtype of ALL. The preliminary research on the fusion gene EP300-ZNF384 suggests it can influence the B cell differentiation and induce leukemia in transgenic mouse model, suggesting that this fusion is closely related to a specific type of ALL, but the mechanism is still unclear. This project focuses on the function of EP300-ZNF384 in ALL, and intends to conduct a series of studies based on in vitro and mouse leukemia model, to further explore the changes of cell phenotype caused by EP300-ZNF384 and the regulation of its underlying signaling pathways, and to reveal the molecular mechanism in the development of leukemia. It is expected that the results of this study will not only enhance our understanding of the pathological mechanism of ALL, but also provide a valuable target for the stratified diagnosis and treatment of ALL.