多发性骨髓瘤（MM）是一种目前仍无法治愈的血液系统恶性肿瘤。MM细胞可能通过自噬途径处理过量累积的毒性蛋白以保护自身存活。DEPTOR是新近发现的mTOR特异性抑制蛋白，我们的前期研究证实DEPTOR在调控MM细胞凋亡及对细胞毒药物敏感性的影响起着重要作用，还证实了DEPTOR表达水平与其自噬活性明显相关。由于肿瘤自噬活性的变化可对其微环境血管新生进行重塑，我们推测DEPTOR可能可通过介导骨髓瘤细胞自噬活性变化重塑肿瘤微环境的血管新生。本项目研究原代骨髓瘤细胞DEPTOR表达水平和自噬活性差异的临床意义及与血管新生作用的关系；探讨DEPTOR表达介导的MM细胞自噬活性变化对内皮细胞功能的影响，并采用基因芯片技术检测内皮细胞血管新生相关基因谱的变化；在体内实验中研究DEPTOR表达水平介导的MM自噬活性变化与肿瘤生长和血管新生的关系，以期为MM的临床治疗提供新靶点和新治疗策略。

Multiple myeloma (MM) remains an incurable hematologic malignant disease. MM cells may protect themselves against accumulation of toxic protein by means of autophagy. DEPTOR is a newly identified specific inhibitor of mTOR and highly expressed in MM cells. Our previous study has shown that DEPTOR might affect myeloma cell sensitivity to cytotoxic agents, and its expression level was closely related to autophagic activity. Because modified autophagic activity of tumor cells may remold angiogenesis of microenvironment, we speculate that DEPTOR may remold tumor microenvironment angiogenesis by means of mediating myeloma cells autophagy. In this study, we will study the clinical significance of DEPTOR expression level and autophagic activity of primary MM cells and make out their relationship with bone marrow angiogenesis. We will explore the effect of modified myeloma cells autophagic activity on the functions of co-cultured endothelial cells and examine angiogenesis gene expression of endothelial cells by microarray technique. We will investigate the influence of DEPTOR-mediated autophagic activity of myeloma cells on tumor proliferation and angiogenesis in vivo. This study is expected to provide new target and strategy for treatment of MM.