利用高通量基因筛选技术在急性髓系白血病中的治疗靶点发现。

Therapeutic Target Discovery Using High-Throughput Genetic Screens in Acute Myeloid Leukemia.

机构信息

Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou 350108, China.

Union Clinical Medical College, Fujian Medical University, Fuzhou 350108, China.

出版信息

Cells. 2020 Aug 12;9(8):1888. doi: 10.3390/cells9081888.

DOI:10.3390/cells9081888

PMID:32806592

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7465943/

Abstract

The development of high-throughput gene manipulating tools such as short hairpin RNA (shRNA) and CRISPR/Cas9 libraries has enabled robust characterization of novel functional genes contributing to the pathological states of the diseases. In acute myeloid leukemia (AML), these genetic screen approaches have been used to identify effector genes with previously unknown roles in AML. These AML-related genes centralize alongside the cellular pathways mediating epigenetics, signaling transduction, transcriptional regulation, and energy metabolism. The shRNA/CRISPR genetic screens also realized an array of candidate genes amenable to pharmaceutical targeting. This review aims to summarize genes, mechanisms, and potential therapeutic strategies found via high-throughput genetic screens in AML. We also discuss the potential of these findings to instruct novel AML therapies for combating drug resistance in this genetically heterogeneous disease.

摘要

高通量基因操作工具的发展，如短发夹 RNA(shRNA)和 CRISPR/Cas9 文库，使对导致疾病病理状态的新型功能基因的强有力特征成为可能。在急性髓细胞白血病(AML)中，这些遗传筛选方法已被用于鉴定以前在 AML 中作用未知的效应基因。这些与 AML 相关的基因集中在介导表观遗传学、信号转导、转录调控和能量代谢的细胞途径上。shRNA/CRISPR 遗传筛选还实现了一系列可用于药物靶向的候选基因。本综述旨在总结通过 AML 高通量遗传筛选发现的基因、机制和潜在的治疗策略。我们还讨论了这些发现为对抗这种遗传异质性疾病的耐药性提供新的 AML 治疗方法的潜力。