多发性骨髓瘤代谢重编程研究进展

Research Progress in Metabolic Reprogramming in Multiple Myeloma

多发性骨髓瘤(MM)是一种以骨髓克隆性浆细胞异常增生为特征的恶性疾病。与大多数肿瘤细胞一样,为了满足自身快速繁殖的需要,MM细胞与肿瘤微环境(TME)中的其他细胞竞争营养物质,导致TME中免疫细胞缺氧及能量供给相对缺乏,进而致MM细胞在葡萄糖和谷氨酰胺代谢过程中的靶向途径异常活跃,如葡萄糖转运蛋白和谷氨酰胺转运蛋白表达上调以及缺氧诱导因子-1、c-Myc和磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路激活均可促进糖酵解和谷氨酰胺代谢,而这种代谢重编程效应在MM中尤为显著。因此,深入研究MM代谢重编程的机制,可以为疾病的治疗提供新方向。

Multiple myeloma(MM)is a malignant disease characterized by clonal plasma cell dysplasia of bone marrow.Like most tumor cells,they can compete with other cells in tumor microenvironment(TME)for nutrients in order to meet their own needs for rapid reproduction,resulting in hypoxia of immune cells and relative lack of energy supply in TME,which makes MM abnormally active in various targeted pathways in the process of glucose and glutamine metabolism.The up-regulation of glucose transporter and glutamine transporter expression and the activation of hypoxia-inducible factor-1,c-Myc and phosphatidylinositol-3-kinase/proteinkinases B/mammalian rapamycin target protein signaling pathway can all promote glycolysis and glutamine metabolism,and this metabolic reprogramming effect is particularly reflected in MM.Therefore,in-depth study of the mechanism of MM metabolism reprogramming can provide a new direction for the disease treatment.