Umerez Maitane, Garcia-Obregon Susana, Martin-Guerrero Idoia, Astigarraga Itziar, Gutierrez-Camino Angela, Garcia-Orad Africa
Department of Genetics, Physic Anthropology & Animal Physiology, University of the Basque Country, UPV/EHU, Leioa, Spain.
BioCruces Health Research Institute Pediatric Oncology Group, Barakaldo, Spain.
Pharmacogenomics. 2018 Mar;19(4):361-373. doi: 10.2217/pgs-2017-0164. Epub 2018 Feb 22.
Childhood acute lymphoblastic leukemia survival rates have increased remarkably during last decades due, in part, to intensive treatment protocols. However, therapy resistance and toxicity are still two important barriers to survival. In this context, pharmacoepigenetics arises as a tool to identify new predictive markers, required to guide clinicians on risk stratification and dose individualization. The present study reviews current evidence about miRNA implication on childhood acute lymphoblastic leukemia therapy resistance and toxicity. A total of 12 studies analyzing differential miRNA expression in relation to drug resistance and six studies exploring the association between miRNAs-related SNPs and drug-induced toxicities were identified. We pointed out to miR-125b together with miR-99a and/or miR-100 overexpression as markers of vincristine resistance and rs2114358 in mir-1206 as mucositis marker as the most promising results.
在过去几十年中，儿童急性淋巴细胞白血病的生存率显著提高，部分原因是强化治疗方案。然而，治疗耐药性和毒性仍然是生存的两个重要障碍。在此背景下，药物表观遗传学作为一种工具出现，用于识别新的预测标志物，以指导临床医生进行风险分层和剂量个体化。本研究综述了关于miRNA在儿童急性淋巴细胞白血病治疗耐药性和毒性方面作用的现有证据。共鉴定出12项分析与耐药性相关的差异miRNA表达的研究，以及6项探索miRNA相关单核苷酸多态性与药物诱导毒性之间关联的研究。我们指出，miR-125b与miR-99a和/或miR-100的过表达作为长春新碱耐药性的标志物，以及mir-1206中的rs2114358作为粘膜炎标志物，是最有前景的结果。
