髓外浸润与白血病的复发和难治密切相关。我们分析AML1/ETO+白血病患者资料发现APP高表达者髓外浸润发生率显著升高。前期在kasumi-1细胞证实siRNA干扰APP表达后细胞迁移力降低，对比干扰前后表达谱变化，KEGG分析聚焦于p-ERK/c-Myc/MMP-2通路。同时软件预测APP是miR-144的靶基因，且在不同白血病细胞发现APP与miR-144呈负相关。因此提出假说：miR-144靶向APP通过p-ERK/c-Myc/MMP-2调控AML1/ETO+白血病细胞髓外浸润。本项目拟验证：1)miR-144与白血病髓外转移及生存的相关性，并证实其靶向调节APP；2)APP通过p-ERK/c-Myc/MMP-2调节白血病细胞迁移及对间充质细胞骨髓屏障的调节。此研究将进一步阐明髓外白血病的发生发展机制，明确miR-144和APP是否可作为监测髓外白血病的分子指标，具有重要的临床意义。

Extramedullary infiltration is closely related with leukemia relapse and refractory. We analyzed clinical data of AML1/ETO + leukemia patients and found that patients with high expression of APP got significantly higher incidence of extramedullary infiltration than those who with low expression. In kasumi-1 cell line we found that cell migration was significantly decreased after interference of APP expression. Analyzing the difference of expression profiles between before and after interference, also we used KEGG, at last we focused on p-ERK/c-Myc/MMP-2 pathway.We used software to predict APP gene is the target gene of miR-144. And, we found that there was a negative correlation between APP and miR-144 in different leukemia cells. Therefore, we hypothesized that miR-144 target APP to regulate AML1/ETO + leukemia cells extramedullary infiltration by p-ERK/c-Myc/MMP-2 pathway. This study is designed to identify: 1) the relationship of miR-144 with extramedullary leukemia metastasis and survival, and confirmed miR-144 targets APP; 2) APP through p-ERK/c-Myc/MMP-2 pathway to regulate cell migration and regualte bone marrow mesenchymal cell barrier. This research will further clarify the mechanism of the development of extramedullary leukemia and help us to identify whether miR-144 and APP can be used as markers of extramedullary leukemia or not, it will be very important..