曹慧贞1,孙 航2,孙允霄1*
(1 滨州医学院烟台附属医院儿科,烟台 264100;2 滨州医学院生物化学与分子生物学教研室,烟台 264003)

摘 要:

摘 要:伊马替尼(imatinib, IM) 是BCR-ABL1、KIT 和PDGFR 等多种酪氨酸激酶的抑制剂。90%∼95% 的慢性粒细胞白血病(CML) 含有BCR-ABL 融合基因,85%∼90% 的胃肠道间质瘤(GIST) 存在KIT 或PDGFRA突变,目前IM 主要作为靶向药应用于CML 和GIST,它的问世是CML 和GIST 治疗的重大突破。然而,约30% 的CML 由于耐药或不耐受而停止使用,约50% 的GIST 在治疗后的两年内出现了耐药,因此,了解IM 耐药机制对于解决IM 耐药问题至关重要。miRNA (microRNA, small RNA) 是一类长约22 nt 的非编码RNA,可通过与特定mRNA 结合或调节特定mRNA 的翻译过程来调控基因的表达。许多药物耐药与miRNA 的异常表达有关,miRNA 与IM 耐药是近年来的研究热点,改变miRNA 的表达模式可以有效抑制耐药和应对治疗。该文综述了miRNA 表达与IM 耐药的关系及其作用机制,为解决IM 耐药问题提供了新的思路。

Research progress on the correlation between miRNA and imatinib resistance
CAO Hui-Zhen1, SUN Hang2, SUN Yun-Xiao1*
(1 Department of Pediatrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264100, China; 2 Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai 264003, China)


Abstract: Imatinib (IM) is an inhibitor of various tyrosine kinases such as BCR-ABL1, KIT and PDGFR. 90%∼95% of chronic myeloid leukemia (CML) contains bcr-abl fusion gene, 85%∼90% of gastrointestinal stromal tumors (GIST) has KIT or PDGFRA mutation. At present, IM is primarily used as a targeted drug in CML and GIST. However, about 30% of CML patients have to discontinue treating with IM due to resistance or intolerance to the drug, and about 50% of GIST patients develop resistance within two years after treatment. Therefore, it is important to understand the mechanisms of IM resistance. miRNA (microRNA, small RNA) is a type of non-coding RNA with a length of about 22 nt, which can regulate gene expression by binding to specific mRNA or adjusting the protein translation process of specific mRNA. Many drug resistances are related to the abnormal expression of miRNA, and the relationship of miRNA and IM resistance has been a hot research topic in recent years. Changing expression pattern of miRNA can be effective in response to treatment by inhibiting drug resistance. This article aims to provide new ideas for resolving the problem of IM resistance by reviewing the relationship between miRNA expression and IM resistance and its mechanism of action.

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