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急性髓系白血病中常见突变基因的小鼠模型

Mouse Models of Frequently Mutated Genes in Acute Myeloid Leukemia.

作者信息

Mohanty Sagarajit, Heuser Michael

机构信息

Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.

出版信息

Cancers (Basel). 2021 Dec 8;13(24):6192. doi: 10.3390/cancers13246192.

Abstract

Acute myeloid leukemia is a clinically and biologically heterogeneous blood cancer with variable prognosis and response to conventional therapies. Comprehensive sequencing enabled the discovery of recurrent mutations and chromosomal aberrations in AML. Mouse models are essential to study the biological function of these genes and to identify relevant drug targets. This comprehensive review describes the evidence currently available from mouse models for the leukemogenic function of mutations in seven functional gene groups: cell signaling genes, epigenetic modifier genes, nucleophosmin 1 (), transcription factors, tumor suppressors, spliceosome genes, and cohesin complex genes. Additionally, we provide a synergy map of frequently cooperating mutations in AML development and correlate prognosis of these mutations with leukemogenicity in mouse models to better understand the co-dependence of mutations in AML.

摘要

急性髓系白血病是一种临床和生物学上具有异质性的血癌,其预后和对传统疗法的反应各不相同。全面测序使得在急性髓系白血病中发现了复发性突变和染色体畸变。小鼠模型对于研究这些基因的生物学功能以及确定相关药物靶点至关重要。这篇全面综述描述了目前从小鼠模型中获得的关于七个功能基因组突变致白血病功能的现有证据:细胞信号基因、表观遗传修饰基因、核磷蛋白1()、转录因子、肿瘤抑制因子、剪接体基因和黏连蛋白复合体基因。此外,我们提供了急性髓系白血病发生过程中频繁协同作用突变的协同图谱,并将这些突变的预后与小鼠模型中的致白血病性相关联,以更好地理解急性髓系白血病中突变的相互依赖性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2289/8699817/29e604bf3c3e/cancers-13-06192-g001.jpg

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