早期T细胞前体急性淋巴白血病（early T-cell precursor T-ALL，ETP T-ALL）是近期新发现的一种T-ALL亚型。ETP T-ALL具有微小残留高，预后差，存活率低等特点，是一种高危难治的T-ALL亚型。文献报道组蛋白甲基化复合物Polycomb Repressive Complex 2（PRC2）在ETP T-ALL中有较高的突变率。ETP T细胞来源于骨髓，是成熟T细胞的祖细胞。我们的前期研究发现PRC2在正常ETP T细胞的维持中起重要作用。因此在本研究中我们拟利用PRC2组分EZH2敲除小鼠探索PRC2在正常ETP维持和分化中的作用。并筛选ETP T-ALL病例，在病人标本中验证ETP T细胞中受PRC2调节的蛋白和信号通路是否在ETP T-ALL中发生变化，揭示PRC2在ETP T-ALL发生发展中的作用机制，探索治疗ETP T-ALL的新方法。

Early T-cell precursor (ETP) leukaemias have been recently recognized as a form of T-cell acute lymphoblastic leukaemia (T-ALL) with a poor prognosis. Whole genome sequencing of 12 ETP ALL cases revealed that over 40% of ETP T-ALL cases harboured mutations in genes encoding components of the polycomb repressor complex 2 (PRC2), indicating PRC2 play a key role in ETP T-ALL. The normal ETP thymocyte, originated from hematopotic stem cells, retains the ability to differentiate into mature T cells. Our previous results revealed that PRC2 is important for the maturation of T cells. In this project, we plan to figure out the role of PRC2 in the maintenance and differentiation of ETP T cells and find the targets and signaling pathways regulated by PRC2 in ETP T cells. These results will help to reveal the role of PRC2 played in ETP T-ALL and establish the new methods to treat ETP T-ALLs.