叶酸代谢与儿童急性淋巴细胞白血病耐药复发的研究进展  

Research progress of folic acid metabolism and relapse of drug resistance in childhood acute lymphoblastic leukemia

作　　者：王树轩 许岩 陈尧[1] 方后顺 李慧[1] WANG Shuxuan;XU Yan;CHEN Yao;FANG Houshun;LI Hui(Key Laboratory of Pediatric Hematology&Oncology National Health Commission,Pediatric Translational Medicine Institute,Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心,卫生健康委员会儿童血液肿瘤重点实验室,儿科转化医学研究所,上海200127

出　　处：《生命的化学》2020年第10期1700-1707,共8页Chemistry of Life

基　　金：国家自然科学基金项目(81870116);上海市科委“青年科技启明星”计划(18QA1402900);上海市卫健委“新优青”计划(2017YQ032)。

摘　　要：随着医疗技术的提高与新型药物的研发,儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的治愈率显著提高,但是一旦出现耐药或复发,长期生存率则会较低并发生预后不良。因此,耐药复发是儿童ALL治疗的瓶颈,也是导致治疗失败和死亡的首要因素。叶酸拮抗剂类药物是ALL常用的化学治疗药物之一,旨在特异性阻断叶酸代谢途径中的各种酶,从而显著减少叶酸储存并扰乱核苷酸的生物合成,诱导快速分裂的细胞凋亡。本文总结了叶酸拮抗剂类药物治疗中产生耐药的主要机制,以期为克服其耐药提供新的思路和策略,进一步减少儿童ALL患者的复发比例,提高治愈率。Relapsed acute lymphoblastic leukemia remains poor prognosis which caused by drug resistance,in spite of risk-stratified combination therapy and improved cure rate.Therefore,drug resistance and relapse is the bottleneck in ALL treatment and also the leading causes of mortality among all childhood malignancies.Antifolates are the most common chemotherapeutic drugs used in ALL treatment,which were designed to specifically block various enzymes in the folate metabolic pathway,thus markedly reducing folate pools and disrupting nucleotide biosynthesis.In this review,we summarized the mechanisms of drug resistance in antifolates,which can provide new ideas and therapeutic strategies for overcoming drug resistance to reduce the ALL relapse and improve cure rate.

关 键 词：急性淋巴细胞白血病 叶酸代谢 叶酸拮抗剂 耐药 

分 类 号：R733.71[医药卫生—肿瘤]