上海交通大学学报(医学版)

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急性淋巴细胞白血病硫嘌呤类药物耐药机制的研究进展

方后顺1,2, 李慧2, 杨帆2, 艾晓杰1, 周斌兵2   

  1. 上海交通大学 1.农业与生物学院, 上海市兽医生物技术重点实验室, 上海 201101; 2.医学院附属儿童医学中心, 卫生部儿童血液肿瘤重点实验室, 儿科转化医学研究所, 上海 200127
  • 出版日期:2016-10-28 发布日期:2016-11-29
  • 通讯作者: 周斌兵, 电子信箱: binbing_s_zhou@yahoo.com。艾晓杰, 电子信箱: xjai@sjtu.edu.cn。
  • 作者简介:方后顺(1989—), 男, 硕士生; 电子信箱: fanghoushun19@126.com。
  • 基金资助:

    国家自然科学基金(81500112)

Research progresses of the mechanisms of thiopurine resistance in acute lymphoblastic leukemia

FANG Hou-shun1,2, LI Hui2, YANG Fan2, AI Xiao-jie1, ZHOU Bin-bing2   

  1. 1.School of Agriculture and Biology, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai Jiao Tong University, Shanghai 201101, China; 2.Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Childrens Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2016-10-28 Published:2016-11-29
  • Supported by:

    National Natural Science Foundation of China, 81500112

摘要:

硫嘌呤类药物是急性淋巴细胞白血病(ALL)治疗缓解期的常用化学治疗药物之一,其在体内需经代谢转化成具有生物活性的巯基鸟嘌呤核苷酸,发挥杀死肿瘤细胞的作用。一旦硫嘌呤类药物在体内代谢通路中的关键酶存在单核苷酸多态性或发生功能突变,肿瘤细胞就会耐受硫嘌呤类药物而产生耐药复发。该文总结了ALL硫嘌呤类药物耐药相关代谢酶突变的研究进展,以期为克服其耐药提供新的思路和策略。

关键词: 急性淋巴细胞白血病, 硫嘌呤类药物, 药物耐药, 代谢酶

Abstract:

Thiopurine is one type of common chemotherapy drugs for the treatment of acute lymphoblastic leukemia (ALL) during remission. It must be metabolized and transformed to thioguanine nucleotides in vivo, which have the biological activity for killing tumor cells. Once key enzymes in thiopurine metabolic pathway develop single nucleotide polymorphisms or functional mutations, tumor cells will become resistant to thiopurine treatment and relapse will occur quickly. This article summarizes research progresses of metabolic enzyme mutations, which contribute to the thiopurine resistance in ALL, in order to provide novel ideas and strategies for overcoming the thiopurine resistance.

Key words: acute lymphoblastic leukemia, thiopurine, drug resistance, metabolic enzymes