SIRT3在白血病耐药中作用的研究进展

Recent advances in the role of SIRT3 in leukemia drug resistance

白血病是一类源自异常造血干/祖细胞的恶性克隆性疾病,解决其化学治疗中的耐药问题是白血病治疗的关键。SIRT3是主要的线粒体NAD+依赖性去乙酰化酶,可靶向调节多种代谢途径的酶和转录因子,在肿瘤中具有双重作用。在白血病细胞中活性氧簇(reactive oxygen species,ROS)水平和其耐药性紧密关联。SIRT3可通过多种途径降低ROS水平,增强肿瘤细胞对于氧化应激的应对能力,从而维持其生存。而在SIRT3去乙酰化酶活性降低时,这一作用减弱,使得肿瘤对于治疗药物更加敏感。通过研究SIRT3在白血病耐药中的作用,可能找到新的白血病治疗的靶点。该文综述了SIRT3在白血病耐药中作用的研究进展。

Leukemia is a clonal malignant disease originating from abnormal hematopoietic stem cells or progenitor cells. The key issue of leukemia treatment is its drug-resistance. SIRT3 is the main mitochondrial NAD + dependent deacetylase. It regulates enzymes and transcription factors of many metabolism pathways. SIRT3 acts both as oncogenic gene and tumor-suppressing gene in the oncogenesis of different cancers. Studies have shown that reactive oxygen species (ROS) level is closely related to drug resistance of cancer cells. ROS level is elevated in leukemia cells, thus affecting its drug resistance. SIRT3 can downregulate ROS level in many ways and enhance cell survival in the case of oxidative stress. Decreased deacetylase activity of SIRT3 makes leukemic cells more vulnerable to oxidative stress so that they are more sensitive to current chemotherapies. Through discovering the function of SIRT3 in leukemia cells, a chance of finding a new target for leukemia treatment can be found. This article reviews recent advances on the role of SIRT3 in leukemia drug resistance.