Association of microRNA Polymorphisms with Toxicities Induced by Methotrexate in Children with Acute Lymphoblastic Leukemia.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2023-11-20 DOI:10.3390/hematolrep15040065

Vasiliki Karpa, Kallirhoe Kalinderi, Liana Fidani, Athanasios Tragiannidis

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Abstract

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5'-regulatory regions of genes. Recent studies have demonstrated a significant role of microRNAs (miRNAs) in the transport and metabolism of drugs and in the regulation of target genes. In the last few years, the number of annotated miRNAs has continually risen, in addition to the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.

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急性淋巴细胞白血病患儿甲氨蝶呤诱导的microRNA多态性与毒性的关系

甲氨蝶呤(MTX)是一种与叶酸结构相关的物质，是一种重要的化疗药物，几十年来一直用于治疗儿童急性淋巴细胞白血病(ALL)和其他类型的癌症，如非霍奇金淋巴瘤和骨肉瘤。尽管观察到成功的结果，但主要的缺点是患者之间药代动力学和药效学的可变性。与其使用相关的主要不良事件是肾毒性、粘膜炎和骨髓抑制，特别是在高剂量使用时。与甲氨蝶呤相关的潜在不良反应和毒性引起关注，并可能导致剂量减少或治疗中断。MTX转运基因的遗传变异与毒性有关。过去的药物遗传学研究主要集中在基因编码区和5'调控区的单核苷酸多态性(snp)上。最近的研究表明，microRNAs (miRNAs)在药物的转运和代谢以及靶基因的调控中发挥着重要作用。在过去的几年中，除了对miRNA多态性和MTX毒性的研究外，注释miRNA的数量也在不断增加。因此，本研究的目的是探讨与MTX不良反应相关的miRNA变异的作用。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.