上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (2): 211-217.doi: 10.3969/j.issn.1674-8115.2022.02.012

• 综述 • 上一篇    

儿童急性淋巴细胞白血病化学治疗常规药物耐药机制的研究进展

林艳艳(), 许岩, 李慧()   

  1. 上海交通大学医学院附属上海儿童医学中心儿科转化医学研究所,国家卫生健康委员会儿童血液肿瘤重点实验室,上海 200127
  • 收稿日期:2021-09-06 出版日期:2022-02-28 发布日期:2022-03-17
  • 通讯作者: 李慧 E-mail:lyy18951897@126.com;lihui@scmc.com.cn
  • 作者简介:林艳艳(1997—),女,硕士生;电子信箱:lyy18951897@126.com
  • 基金资助:
    国家自然科学基金(81870116);上海市科学技术委员会“青年科技启明星”计划(18QA1402900)

Progress in research on the mechanism of drug resistance to conventional chemotherapeutic drugs in children with acute lymphoblastic leukemia

Yanyan LIN(), Yan XU, Hui LI()   

  1. Key Laboratory of Pediatric Hematology and Oncology of National Health Commission, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Received:2021-09-06 Online:2022-02-28 Published:2022-03-17
  • Contact: Hui LI E-mail:lyy18951897@126.com;lihui@scmc.com.cn
  • Supported by:
    National Natural Science Foundation of China(81870116);Rising-Star Program from the Science and Technology Commission of Shanghai Municipality(18QA1402900)

摘要:

急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)在儿童血液肿瘤中发病率最高,占比约为所有儿童癌症的三分之一。随着治疗方案的不断优化和我国医疗保障水平的持续提升,儿童ALL的治疗效果取得了显著的改善,5年以上总体生存率可达90%。然而临床耐药复发的出现且有效治疗手段的欠缺,导致患儿的生存期和生活质量严重下降。近年来,ALL耐药的发病和调控机制成为国内外研究的热点和难点。研究表明,ALL患儿不仅可能对某一种化学治疗(化疗)药物产生耐药,更可能存在多重耐药的棘手情况。因此,完善ALL耐药机制的研究,对改善ALL患儿的预后有重要意义。该文从儿童ALL治疗的常规化疗药物入手,回顾相关化疗药物耐药的既往文献,分别对激素类、抗代谢类(叶酸拮抗剂类、硫嘌呤类、促氨基酸代谢类)、生物碱类、蒽环类在内的多种药物耐药机制的研究现状进行综述,以期为应对儿童ALL化疗常规药物临床耐药问题提供理论基础。

关键词: 急性淋巴细胞白血病, 儿童, 化学治疗, 耐药机制, 复发

Abstract:

Acute lymphoblastic leukemia (ALL) has the highest incidence of hematological tumors in children, accounting for about one-third of all childhood cancer cases. With the continuous optimization of the treatment plan and the expansion of health care coverage in China, remarkable improvements have been achieved in the treatment of childhood ALL, and the overall survival rate of more than 5 years has reached 90%. Lack of effective treatment and unacceptably high recurrence rate are the leading causes of severe decrease in the survival and quality of life of children with drug resistance. In recent years, pathogenesis and regulation mechanism of ALL drug resistance has become a hot topic and a difficulty of research at home and abroad. Studies have shown that children with ALL may not only antagonize a certain chemotherapy (chemotherapeutic) drug, but also have a thorny situation of multi-drug resistance. Therefore, it is of great significance to improve the research on the mechanism of drug resistance of ALL to improve the prognosis of children with ALL. This review summarizes recent research progress in drug resistance mechanisms of conventional chemotherapy drugs for childhood ALL, including hormones, antimetabolite drugs (folate antagonists, thiopurines, and amino acid metabolizing drugs), alkaloids and anthracyclines, in order to provide theoretical basis for coping with clinical drug resistance.

Key words: acute lymphoblastic leukemia, child, chemotherapy, drug-resistance mechanism, recurrence

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