DNMT3A突变，是一种在急性髓系白血病（AML）中新发现的体细胞获得性突变，作为强烈提示白血病复发的独立危险因素，主要聚集在中危/正常核型急性髓系白血病（CN-AML）中，而882精氨酸位点点突变是最常见的突变形式。鉴于其使白血病预后更差的具体分子机制尚不明晰，不同区域协作组进行了大样本急性髓系白血病的回顾性研究，结果表明DNMT3A突变阳性组与DNMT3A突变阴性组基因表达谱数据不尽相同，甲基化水平和模式不一，其根本原因可能归结于遗传背景及个体差异。因此，本项目用锌指核酸酶技术人工构建了DNMT3A882突变的细胞模型，拟运用表达谱芯片及全基因组甲基化芯片筛选DNMT3A突变模型中异常表达的基因，通过体内和体外实验寻找DNMT3A突变下游相关调控靶点，从而识别因DNMT3A突变导致AML较差预后的关键靶标，进而为准确进行AML分层诊断、DNMT3A的临床干预及靶向治疗提供新的理论基础。

DNMT3A mutation, as an independent risk factor strongly forecast the recurrence, is a fresh somatic cell acquired mutations found in acute myeloid leukemia (AML). The mutation gathers in the normal karyotype/acute myeloid leukemia (CN-AML), and the point mutation of arginine locating in 882 is the most common form. Because the specific molecular mechanism of the worse prognosis of leukemia is still not clear, different areas of large sample of acute myeloid leukemia retrospective studies reported various results in the gene expression profiles, methylation level and model by comparing the positive to the negative in DNMT3A mutation. The fundamental reason may origin from the genetic background and individual difference. From this point, we apply zinc finger nucleic acid enzyme technology to construct a vitro model with DNMT3A882 mutation, which base on a kind of cell line. Later, we intend to select cell clone with the DNMT3A mutations, and analyse the information from profiling chip and whole genome methylation chip. Then, looking for the related downstream controlling gene by in vivo and in vitro experiments, so as to recognize the special target related to DNMT3A mutations in the AML prognosis,and provide the new theoretical foundation to accurate stratification diagnosis and targeted therapy for AML.