化疗相关性高血糖是成人急性ALL复发和高死亡率的独立危险因素，其与儿童ALL预后关系未明，强化胰岛素治疗对预后的影响未知。本课题组前期研究显示化疗相关性高血糖在儿童ALL中发生率17.62%，高血糖组复发率和死亡率显著增高，胰岛素通过活化AKT/mTOR促进成人ALL细胞生长，同时增加柔红霉素耐药性，并上调IR、IGF-ⅠR表达。IGF-1是AKT/mTOR通路的上游调节因子，由此我们认为IGF-1可能通过AKT/mTOR途径促进儿童ALL细胞生长而影响复发。本项目拟采用前瞻性随机对照研究，探讨儿童ALL发生化疗相关性高血糖的危险因素，体外实验研究胰岛素对不同ALL细胞株和原代儿童ALL细胞生长、凋亡和耐药等的影响，研究IGF-1激活AKT/mTOR途径对儿童ALL复发的影响和IGF-1R在白血病细胞中的表达模式，探讨抗IGF-1R单抗的潜在靶向治疗作用

Chemotherapy related hyperglycemia is an independent risk factor for early relapse and high mortality during adult ALL, but whether it affects the outcomes of childhood ALL remains unclear, and also the insulin treatment. Our studies show the incidence rate of chemothreapy-related hyperglycemia happened on children is 17.62% and which has higher relapse rate and mortality, insulin promotes the growth of ALL cells in adult by activating AKT/mTOR pathway、increases the tolerance of DNR and up-regulate the mRNA level of IR and IGF-1R. As an upstream regulator factor of AKT/mTOR pathway, we draw to the conclusion that IGF-1 may promote the growth of ALL cells and induced relapse. we aim to collect large samples of clincal data of ALL patients to evaluate the risk factors of chemotherapy related hyperglycemia. Trough vivo experiment, we explore the role of insulin in the proliferation, apoptosis and resistance of chemothreapy in ALL cell lines, study the IGF's affection in the prognosis of ALL through the pathway of AKT/mTOR, investigate the expression characteristic IGF-I R in ALL cell lines, and explore the effect of lGF-IR monoclonal antibody(IGF-IR MAb) as a promising target in the therapy of ALL.