靶向铁稳态治疗白血病的策略转变:从铁螯合到铁过载诱导铁死亡  

The strategy change of targeting iron homeostasis for leukemia therapy:from iron chelation to iron overload as a therapeutic strategy to induce ferroptosis

作　　者：郑湧智 陈艳欣[1] 胡建达[1] Zheng Yongzhi;Chen Yanxin;Hu Jianda(Department of Hematology,Fujian Medical University Union Hospital,Fujian Institute of Hematology,Fujian Provincial Key Laboratory on Hematology,Fuzhou 350001,China)

机构地区：[1]福建医科大学附属协和医院血液科,福建省血液病研究所,福建省血液病学重点实验室,福州350001

出　　处：《白血病．淋巴瘤》2022年第7期441-444,共4页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金青年项目(82000142)。

摘　　要：铁是生命不可缺少的元素,参与各种重要的生理活动。由于铁的潜在毒性,人体具有严格的铁代谢调节机制来维持体内铁稳态。铁代谢失调及过量铁积累与白血病的发生、发展密切相关。由于铁的促氧化性质及其对DNA的破坏作用,过量的铁会促进白血病的发展,而且白血病细胞比正常细胞需要获得更多的铁来维持快速生长和增殖,即"铁成瘾"。铁螯合剂可清除白血病细胞内的铁,诱导白血病细胞分化和凋亡。然而"铁成瘾"使得白血病细胞更易受铁过载影响,对一种铁离子介导的细胞死亡形式——铁死亡更加敏感。根据白血病细胞和正常细胞对铁的不同需求,通过铁过载来选择性杀死白血病细胞的方法有望成为白血病治疗的新策略,文章就靶向铁稳态治疗白血病的策略进行综述。Iron,an indispensable element for life,is involved in all kinds of vital physiological activities.Due to its potential toxicity,the body has a strict regulation mechanism of iron metabolism to maintain the"iron homeostasis".Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia.Specifically,due to the pro-oxidative nature of iron and its damaging effects on DNA,excess iron promotes the progression of leukemia;on the other hand,leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation,which is known as"iron addiction".Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells.However,"iron addiction"makes leukemia cells more susceptible to iron overload,and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis.According to the different needs of leukemia cells and normal cells for iron,the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment.This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

关 键 词：铁代谢障碍 白血病 铁螯合剂 谷胱甘肽转移酶 

分 类 号：R733.7[医药卫生—肿瘤]