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[EVI1在正常造血及造血系统恶性肿瘤中的作用与调控]

[The role and regulation of EVI1 in normal hematopoiesis and hematopoietic malignancies].

作者信息

Masamoto Yosuke

机构信息

Department of Cell Therapy & Transplantation Medicine, The University of Tokyo Hospital.

出版信息

Rinsho Ketsueki. 2024;65(9):954-960. doi: 10.11406/rinketsu.65.954.

Abstract

EVI1 is a zinc finger transcription factor encoded by the MECOM locus and is essential for the development and maintenance of hematopoietic stem cells. However, overexpression of EVI1 in various myeloid malignancies is associated with aggressive clinical behavior and poor outcome. The locus encodes multiple isoforms that are differentially acting and independently regulated. EVI1 interacts with a variety of transcription and epigenetic factors via different domains. It also regulates cell survival, differentiation, and proliferation through a variety of mechanisms, including transcriptional activation and repression, regulation of other transcription factors' activity, and chromatin remodeling. While the mechanism by which 3q26 translocation leads to high EVI1 expression through enhancer hijacking of genes active in myeloid development is now better understood, regulation of EVI1 expression in the absence of chromosomal translocations and in normal hematopoiesis remains unclear. Recent studies have provided insight into the regulatory mechanisms of EVI1 expression and action, which may lead to development of targeted therapies in the near future.

摘要

EVI1是一种由MECOM基因座编码的锌指转录因子,对造血干细胞的发育和维持至关重要。然而,EVI1在各种髓系恶性肿瘤中的过表达与侵袭性临床行为和不良预后相关。该基因座编码多种亚型,它们具有不同的作用且受到独立调控。EVI1通过不同结构域与多种转录和表观遗传因子相互作用。它还通过多种机制调节细胞存活、分化和增殖,包括转录激活和抑制、调节其他转录因子的活性以及染色质重塑。虽然现在对3q26易位通过劫持在髓系发育中活跃的基因增强子导致EVI1高表达的机制有了更好的理解,但在无染色体易位情况下以及正常造血过程中EVI1表达的调控仍不清楚。最近的研究为EVI1表达和作用的调控机制提供了见解,这可能在不久的将来促成靶向治疗的发展。

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