坏死性凋亡的机制及其治疗白血病的研究进展

白血病是造血干细胞恶性克隆性疾病.近年来,随着化疗、造血干细胞移植、分子靶向治疗等多种治疗方法的快速发展,使白血病患者的完全缓解(CR)率及5年无病生存(EFS)率均较前有所改善,但仍有大部分白血病患者出现耐药和复发.目前,临床上大部分化疗药物及分子靶向药物都是通过诱导白血病细胞发生凋亡,以达到治疗目的.因此,寻找有效逆转凋亡耐受的方法改善白血病患者的预后,成为当务之急.坏死性凋亡(necroptosis)为近年来新发现的一种细胞死亡形式,以细胞出现程序性坏死样改变为特征.诱导白血病细胞发生坏死性凋亡,有望成为凋亡诱导失败,以及其他形式的耐药白血病患者的新治疗策略.笔者将针对近年来坏死性凋亡与白血病治疗的相关研究进展进行阐述.

Mechanisms of necroptosis and its research progress in leukemia treatment

Leukemia is a malignant clonal disorder of hematopoietic stem cells.Recently,the great development of leukemia treatment such as chemotherapy,hemopoietic stem cell transplantation and molecular targeted therapy have significantly improved the rate of patients achieving complete remission (CR) or 5-year event free survival (EFS).Meanwhile,high rates of relapse and drug resistance pose an enormous challenge to us.As the majority of chemotherapeutic and targeted drugs kill leukemia cells through apoptosis induction.We propose that an agent inducing non-apoptotic cell death may overcome drug resistance and induced cell death.Necroptosis is a newly found programmed cell death characterized with morphology of necrotic cell death.Therefore,inducing necroptosis of leukemia cells may have significant potential in leukemia therapy for patients who were failure of apoptosis induction or drug resistance.The author summarizes the research progress on intra-cellular regulation mechanism of necroptosis and its induction in leukemia cells.