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BET在血液系统肿瘤中的作用:免疫、发病机制、临床试验及药物联合应用

BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.

作者信息

Ma Tao, Chen Yan, Yi Zhi-Gang, Li Yan-Hong, Bai Jun, Li Li-Juan, Zhang Lian-Sheng

机构信息

Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Department of Hematology, Lanzhou University Second Hospital, Lanzhou, Gansu 730000, China.

出版信息

Genes Dis. 2022 Mar 28;10(6):2306-2319. doi: 10.1016/j.gendis.2022.03.004. eCollection 2023 Nov.

Abstract

The bromodomain and extra-terminal (BET) proteins act as "readers" for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes. BET protein is associated with transcriptional elongation of genes such as and , and is involved in the regulation of cell cycle and apoptosis. Meanwhile, BET inhibitors (BETi) have regulatory effects on immune checkpoints, immune cells, and cytokine expression. The role of BET proteins and BETi in a variety of tumors has been studied. This paper reviews the recent research progress of BET and BETi in hematologic tumors (mainly leukemia, lymphoma and multiple myeloma) from cellular level studies, animal studies, clinical trials, drug combination, etc. BETi has a promising future in hematologic tumors, and future research directions may focus on the combination with other drugs to improve the efficacy.

摘要

溴结构域和额外末端(BET)蛋白作为赖氨酸乙酰化的“读取器”,促进转录延伸复合物的募集。BET蛋白与诸如[具体基因1]和[具体基因2]等基因的转录延伸相关,并参与细胞周期和细胞凋亡的调控。同时,BET抑制剂(BETi)对免疫检查点、免疫细胞和细胞因子表达具有调节作用。BET蛋白和BETi在多种肿瘤中的作用已得到研究。本文从细胞水平研究、动物研究、临床试验、药物联合等方面综述了BET和BETi在血液系统肿瘤(主要是白血病、淋巴瘤和多发性骨髓瘤)中的最新研究进展。BETi在血液系统肿瘤中具有广阔的前景,未来的研究方向可能集中在与其他药物联合以提高疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ae/10404881/38b7bf98eb56/gr1.jpg

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