Pig7基因编码的SIMPLE蛋白为早期内体/溶酶体膜固有蛋白，目前普遍认为其参与泛素-溶酶体介导的细胞蛋白分选和降解过程。我们前期工作发现在急性白血病患者(包括难治/复发患者)及白血病细胞系(包括耐药株)中该基因表达明显下调，同时证实高表达外源性pig7的白血病细胞(包括耐药株)对药物的敏感性明显增高。本研究旨在进一步探明上述pig7介导的白血病细胞药物增敏作用是否与溶酶体介导的细胞凋亡相关，SIMPLE蛋白是否通过溶酶体途径调控了细胞内凋亡相关信号通路，MRP1、Pgp等ABC系统的是否参与了此增敏过程， SIMPLE蛋白所在的内体/溶酶体是否通过释放溶酶体酶参与调控上述过程，而在此过程中SIMPLE蛋白细胞内定位改变是否具有普遍性，是否作为某种细胞内信号参与调控了溶酶体活性？阐明pig7在逆转白血病耐药和在调节细胞分化凋亡中的作用机制，可以为白血病的靶向治疗提供新的靶向分子。

SIMPLE protein eccoded by Pig7 gene has been proved to be one of integral proteins in early endosome/lysosomeearly, and is responsible for the sorting and degradation of intracellular proteins. we revealed a markedly decreased pig7 expression in AL patient group (including relapsed/refractory patients) and AL cell lines (including MDR cell lines), and demonstrated ectopic expression of PIG7 could sensitize leukemia cell lines to chemotherapy medicine, which could then be abrogated by downregulation of PIG7 expression.This study aims to further explore whether that sensitizing effect is associated with intracellular signaling pathways, whether MRP1,Pgp and other ABC systems are involved in this process, whether lysosomal enzymes relaesed by endosome/lysosome where SIMPLE located regulate that process, and whether the intracellular lcalization of SIMPLE protein changes in that regulation? Clarifying the mechanism of sensitizing effect of pig7 in acute leukemia cells may provide a new targeted molecular therapy for leukemia.