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EZH2在急性髓系白血病中的表观遗传作用。

The epigenetic role of EZH2 in acute myeloid leukemia.

作者信息

Fang Jinyong, Zhang Jingcheng, Zhu Lujian, Xin Xiaoru, Hu Huixian

机构信息

Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.

Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.

出版信息

PeerJ. 2024 Dec 6;12:e18656. doi: 10.7717/peerj.18656. eCollection 2024.

Abstract

Acute myeloid leukemia (AML), a malignant disease of the bone marrow, is characterized by the clonal expansion of myeloid progenitor cells and a block in differentiation. The high heterogeneity of AML significantly impedes the development of effective treatment strategies. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), regulates the expression of downstream target genes through the trimethylation of lysine 27 on histone 3 (H3K27me3). Increasing evidence suggests that the dysregulation of EZH2 expression in various cancers is closely associated with tumorigenesis. In the review, we examine the role of EZH2 in AML, highlighting its crucial involvement in regulating stemness, proliferation, differentiation, immune response, drug resistance and recurrence. Furthermore, we summarize the application of EZH2 inhibitors in AML treatment and discuss their potential in combination with other therapeutic modalities. Therefore, targeting EZH2 may represent a novel and promising strategy for the treatment of AML.

摘要

急性髓系白血病(AML)是一种骨髓恶性疾病,其特征是髓系祖细胞的克隆性扩增和分化阻滞。AML的高度异质性显著阻碍了有效治疗策略的发展。zeste同源物2增强子(EZH2)是多梳抑制复合物2(PRC2)的催化亚基,通过组蛋白3赖氨酸27的三甲基化(H3K27me3)调节下游靶基因的表达。越来越多的证据表明,EZH2在各种癌症中的表达失调与肿瘤发生密切相关。在这篇综述中,我们研究了EZH2在AML中的作用,强调了它在调节干性、增殖、分化、免疫反应、耐药性和复发中的关键作用。此外,我们总结了EZH2抑制剂在AML治疗中的应用,并讨论了它们与其他治疗方式联合使用的潜力。因此,靶向EZH2可能是一种治疗AML的新的有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c639/11627098/838e669407e4/peerj-12-18656-g001.jpg

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