摘要
背景:DNA修复途径的缺陷是过多实体瘤的致病因素,但仅在血液系统恶性肿瘤中才刚刚开始探索。基因组不稳定性,包括DNA序列的突变,染色体非整倍性,易位和基因扩增,有助于AML的发展和进展。先前的DNA损伤剂暴露增加了发生AML的风险,遗传综合征的遗传涉及DNA修复途径的改变。此外,这些相同的变化与对一系列化学治疗剂的敏感性和抗性相关。总之,这些研究表明DNA修复途径中的缺陷参与AML的发病机制和预后。 目的:本综述总结了主要的DNA修复途径,并概述了AML中DNA损伤修复异常的现有数据,因为它们与AML中对化疗药物的耐药性和敏感性的发展有关。另外,本文将探讨使用调节这些途径的药物作为AML的新治疗方法。 结论:本综述强调了AML细胞DNA修复机制的异常是AML患者的潜在新型治疗靶点,这些患者对目前的治疗具有抗性。
关键词: 急性髓性白血病,碱基切除修复,化学敏感性,直接酶修复,DNA修复,同源重组,核苷酸切除修复,非同源末端连接。
图形摘要
Current Drug Targets
Title:The Role of DNA Repair Pathways in AML Chemosensitivity
Volume: 19 Issue: 10
关键词: 急性髓性白血病,碱基切除修复,化学敏感性,直接酶修复,DNA修复,同源重组,核苷酸切除修复,非同源末端连接。
摘要: Background: Defects in DNA repair pathways are causal factors for a plethora of solid tumours, but are only just beginning to be explored in haematological malignancies. Genomic instability, including mutations in DNA sequences, chromosomal aneuploidy, translocations and gene amplifications contribute to the development and progression of AML. Prior DNA damaging agent exposure enhances the risk of developing AML, as does inheritance of genetic syndromes that involve alterations in DNA repair pathways. Furthermore, these same variations are associated with sensitivity and resistance to a range of chemotherapeutics. Taken together, these studies suggest that defects within DNA repair pathways are involved in the pathogenesis and prognosis of AML.
Objective: This review summarises the major DNA repair pathways, and presents an overview of current data on DNA damage repair abnormalities in AML as they pertain to the development of resistance and sensitivity to chemotherapeutics in AML. Additionally, the use of drugs that modulate these pathways as new treatments for AML will be explored herein.
Conclusion: This review highlights that abnormalities in DNA repair mechanisms in AML cells are potential novel treatment targets for AML patients with disease that is resistant to current therapies.
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Cite this article as:
The Role of DNA Repair Pathways in AML Chemosensitivity, Current Drug Targets 2018; 19 (10) . https://dx.doi.org/10.2174/1389450119666180110093713
DOI https://dx.doi.org/10.2174/1389450119666180110093713 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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