阐明细胞自噬和程序性坏死的调节机制具有重要的意义，也是生命科学研究热点之一。项目组近年来的系列研究已经证实HMGB1可在多个水平调控白血病细胞自噬进而影响了白血病细胞的多药耐药，并且项目组新近研究发现HMGB1介导的自噬参与了白血病细胞程序性坏死的调控，根据上述发现，申请者提出“HMGB1是调控白血病细胞自噬与程序性坏死动态平衡的关键蛋白”的科学假说，并重点探索内源性和外源性HMGB1介导的自噬途径参与程序性坏死调控的分子机制和信号通路；围绕上述问题，本项目拟选用多个白血病细胞系及SCID小鼠为研究材料，从细胞、分子及动物水平探讨HMGB1介导的白血病细胞自噬与程序性坏死相互影响的机制及核心信号通路。开展本项目研究，可望揭示HMGB1在自噬和程序性坏死动态平衡中的作用新机制，为探求自噬与程序性坏死的关系提供新的实验线索，为白血病的临床防治提供新的思路。

It is important to investigate the mechanisms and crosstalk between autophagy and necroptosis. We have demonstrated that high mobility group box 1 (HMGB1) is an important regulator of autophagy and multidrug resistance in leukemia cells. Our new study also indicated that HMGB1-mediated autophagy is involved in the regulation of necroptosis in leukemia cells. Based on these findings, we hypothesize that HMGB1 is an important regulator linking autophagy and necroptosis. In this study, we will focus on the molecular mechanisms and signal pathways of endogenous HMGB1 and exogenous HMGB1-mediated crosstalk between autophagy and necroptosis in leukemia cells. We will use several leukemia cells and SCID mice to define the mechanism and key signal pathway involving in HMGB1-mediated crosstalk between autophagy and necroptosis. We hope reveal the novel role of HMGB1 in autophagy and necroptosis in leukemia cells, which will provide new ideas for clinical prevention and treatment of leukemia.