作为AML患者的独立预后不良因素，DNMT3A失活性突变促进了AML髓外浸润。国内外研究证实：DNMT3A失活性突变导致HOXA9/HOXA10等多种HOX家族转录因子显著上调，而HOX家族广泛地参与了细胞间及细胞与细胞外基质黏附功能，HOXA10诱导多种黏附分子表达上调，最终促进AML恶性克隆髓外浸润。DNMT3A突变上调HOXA10表达具体机制尚不明确。基于此，本项目拟用CRISPR/Cas9技术构建DNMT3A R882H AML细胞系，通过microRNA芯片、生物信息学等手段，发掘DNMT3A R882H对AML克隆microRNA表达谱的影响，并通过关联分析确定影响HOXA10表达的关键microRNA分子，尝试利用靶向调控手段调节此类microRNA表达，观察对HOXA10高表达的抑制效应，进而阻遏AML恶性克隆的髓外侵袭能力。本研究将为AML靶向治疗及预防复发开辟新的方向。

As an independent inferior prognostic factor of AML patients, DNMT3A mutation was found to enhance the extramedullary infiltration of AML clones. Studies from domestic and abroad have indicated that the silencing mutation of DNMT3A up-regulate a series of HOX-family transcriptional factors, including HOXA9 and HOXA10. HOX family plays important part in the intercellular and cell-matrix adhesion. HOXA10 induces up-regualtion of mutiple adhesive molecules which facilitates the boosted infiltrative ability of AML malignant clones. However, the molecular mechanism of HOXA10 upregulation in DNMT3A mutated AML patients remains elusive. Therefore, we aimed to established DNMT3A R882H SKM1 cell model, and decipher the influences of DNMT3A R882H mutation on microRNA profile of AML clones, especially HOXA10 interacting microRNAs. Through over-expression and silencing shRNA vector, we aimed to inhibit the expression of HOXA10 and hamper the extremedullary infiltration of AML clones, and discover novel therapeutic strategy for AML treatment and relapse prevention.