急性髓细胞白血病是造血系统细胞分化失常引起的恶性疾病。早期急髓细胞里常见的致癌基因DNMT3A, TET2，IDH1/2均为表观基因组重组因子，它们通过影响染色质DNA甲基化水平来引发白血病。地西他滨是在白血病治疗中具有显著疗效的去甲基化表观遗传学药物，然而由于DNA甲基化调控机制广泛作用于染色质的各个区域，并呈细胞类型特异的动态变化，因此至今为止地西他滨的作用靶点和特异性还不清楚。本研究将在急髓细胞里定位地西他滨和多种DNA甲基化调控因子突变下游的基因调控位点， 并在此基础上阐明与去甲基化药物和甲基化调控因子相对应的表观基因组重组的分子机理。本研究还将优化利用少量血液细胞解析肿瘤基因组调控序列的方法，从而探索表观基因组学研究技术在急髓临床检测中的应用。

Acute myeloid leukemia (AML) is a form of cancer that derives from abnormal proliferation and differentiation of cells of the hematopoietic system. Other than one subtype, the acute promyelocytic leukemia (APL), more than 60% of adult patients of AML are not curable. Decitabine is a hypomethylation agent widely used in the treatment of AML, yet its clinical efficacy and specificity remain unclear due to a lack of understanding of the relationship between abnormal DNA methylation patterns and gene regulatory mechanisms. Here we aim to investigate the cis-regulatory elements (CRE) targeted by decitabine in AML cell lines and clinical samples. In parallel, we will map the CREs downstream of epigenetic regulator mutations. By comparing CREs regulated by decitabine and DNA methylation regulator mutations, we will determine the epignenomic changes responding to decitabine in AML, thus providing mechanistic understanding of its clinical efficacy. Finally, we will optimize the protocols in processing blood samples for epigenomic profiling of AML in clinical settings.