急性淋巴细胞白血病（ALL）是儿童最常见的恶性疾病，20%-30%的患儿因耐药或复发而死亡。O-GlcNAc糖基化是近年转录后调控的研究热点，大量与肿瘤相关的蛋白具有O-GlcNAc糖基化修饰。已知PI3K/Akt通路的异常在白血病耐药过程中起关键作用，PI3K/Akt通路和O-GlcNAc糖基化之间存在相互调控关系，而PI3K/Akt通路及其下游的mTOR/c-Myc轴的O-GlcNac糖基化修饰是否参与儿童B-ALL的耐药的发生，目前尚无研究。我们已发现耐药型BALL细胞株Nalm-6的O-GlcNac水平增高，说明白血病细胞耐药与O-GlcNac糖基化相关。我们将分析儿童白血病细胞的糖代谢状况及c-Myc蛋白的O-GlcNac修饰状态，寻找耐药细胞株中调控mTOR/c-Myc信号轴O-GlcNac修饰的关键分子并研究其对耐药相关基因的调控机制，为儿童B-ALL的治疗提供新靶点。

ALL is the most common type of malignant disease among children. About 20%-30% cases died from relapspe or drug resistance of ALL. As a hot topic in post transcriptional regulation in recent years, O-GlcNAc glycosylation modification was found in a large number of tumor associated proteins. It was known that PI3K/Akt pathway play a key role in the process of drug resistance in leukemia, and mutual regulation was found between PI3K/Akt pathway and O-GlcNAc glycosylation, however, the role of O-GlcNAcylation of PI3K/Akt pathway and mTOR/c-Myc Axis in drug resistance of B-ALL has never been reported. We found that the level of O- GlcNAcylation and the expression of OGT increased in drug-resistant B-ALL cell line nalm-6, and confirmed that O- GlcNAcylation participate in the process of drug resistance of B-ALL. We speculated that the O-GlcNAcylation of c-MYC in PI3K/Akt pathway of B-ALL cells paticipated in the regulation of resistance-associated gene. To confirm the hypothesis, we will detect O- GlcNAcylation of mTOR and c-MYC axis in clinical B-ALL B lymphocytes, observe the key molecules in O- GlcNAcylation of mTOR/c-MYC axis, and the regulation mechanism of resistance-associated gene using a variety of molecular biologic techniques. This project will clarify the mechanism of B-ALL multidrug resistance from a new perspective and provide a new target for the treatment of B-ALL.