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TET2 基因突变与急性髓系白血病:生物学、临床意义与治疗启示。

TET2 mutation in acute myeloid leukemia: biology, clinical significance, and therapeutic insights.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 430030, Hubei, China.

出版信息

Clin Epigenetics. 2024 Nov 9;16(1):155. doi: 10.1186/s13148-024-01771-2.

Abstract

TET2 is a critical gene that regulates DNA methylation, encoding a dioxygenase protein that plays a vital role in the regulation of genomic methylation and other epigenetic modifications, as well as in hematopoiesis. Mutations in TET2 are present in 7%-28% of adult acute myeloid leukemia (AML) patients. Despite this, the precise mechanisms by which TET2 mutations contribute to malignant transformation and how these insights can be leveraged to enhance treatment strategies for AML patients with TET2 mutations remain unclear. In this review, we provide an overview of the functions of TET2, the effects of its mutations, its role in clonal hematopoiesis, and the possible mechanisms of leukemogenesis. Additionally, we explore the mutational landscape across different AML subtypes and present recent promising preclinical research findings.

摘要

TET2 是一个关键基因,它调节 DNA 甲基化,编码一种双加氧酶蛋白,在基因组甲基化和其他表观遗传修饰以及造血过程中发挥重要作用。TET2 突变存在于 7%-28%的成人急性髓系白血病(AML)患者中。尽管如此,TET2 突变导致恶性转化的确切机制以及如何利用这些见解来增强 TET2 突变的 AML 患者的治疗策略仍不清楚。在这篇综述中,我们概述了 TET2 的功能、其突变的影响、在克隆性造血中的作用以及白血病发生的可能机制。此外,我们还探讨了不同 AML 亚型的突变全景,并介绍了最近有希望的临床前研究发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4055/11550532/247fd4b58916/13148_2024_1771_Fig1_HTML.jpg

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