表观遗传调控在白血病发生中发挥着重要作用，是目前国际上的研究热点。Uhrf1是一种表观遗传因子，主要通过招募DNMT1实现对DNA甲基化的维持。我们发现Uhrf1在AML中表达升高，同时Uhrf1的高表达与AML复发相关。敲低Uhrf1会延缓小鼠白血病的发病进程，而特异性敲除Uhrf1会阻断小鼠白血病的发展。全基因组甲基化测序和ChIP分析表明Uhrf1主要介导特异性靶基因的甲基化状态而调节白血病的发生。此外，我们还发现了Uhrf1的抑制剂对于白血病具有很好的治疗效果。这些结果表明Uhrf1对白血病的发生和治疗致关重要。为了深入研究UHRF1在白血病的发生和治疗中的作用及其机制，本课题组正在检测在白血病小鼠中条件型敲除UHRF1的表型以及Uhrf1抑制剂在PDX模型中的疗效，并将以此为研究对象，结合主要的细胞生物学、分子生物学和RNA测序技术阐明作用机理，为将来可能的临床应用提供重要依据。

Epigenetic regulation plays an important role in leukemia initiation and progression. Uhrf1, an epigenetic factor, maintains DNA methylation by recruiting DNMT1 to replication forks in S phase of the cell cycle. We found that Uhrf1 is highly expressed in t(8;21) leukemia, which is associated with the high relapse rate of the patients. In a leukemia transplantation mouse model, we found that Uhrf1 knockdown delays leukemogenesis driven by AE9a (a high leukemogenic, short isoform of AE). We generated a conditional Uhrf1 knockout mouse model and applied its fetal liver cells to leukemia transplantation assays.The results illustrated that Uhrf1 deficiency leads to blockage of AE9a leukemia development. WGBS (Whole Genome Bisulfite sequencing) and ChIP assay indicated that Uhrf1 mainly mediate the methylation status of specific target genes which regulate the development of leukemia. In addition, we also found that an inhibitor of Uhrf1 has a good therapeutic effect on leukemia. These results suggested that UHRF1 is critical to the pathogenesis and therapy of leukemia. To investigate the therapeutic strategy for targeting UHRF1 and the underlying mechanism, we are examining the phenotype of conditional knocking out UHRF1in AML mouse models and the therapeutic efficacy of the UHRF1 inhibitor in PDX model. We are also going to use the thechnolgies of cell biology, molecular biology and RNA-seq to understand the mechanism of UHRF1’s function, which will providing the important basis for a potential strategy for therapy of leukemia.