[EVI1在正常造血和造血恶性肿瘤中的作用和调控】。]

Yosuke Masamoto
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引用次数: 0

摘要

EVI1是由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,在各种髓系恶性肿瘤中,EVI1 的过表达与侵袭性临床表现和不良预后有关。该基因座编码多种异构体,这些异构体具有不同的作用和独立的调控。EVI1 通过不同的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的存活、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 3q26 易位通过增强子劫持在骨髓发育中活跃的基因而导致 EVI1 高表达的机制现在已经比较清楚,但在没有染色体易位和正常造血过程中 EVI1 的表达调控仍不清楚。最近的研究深入揭示了 EVI1 表达和作用的调控机制,这可能会在不久的将来开发出靶向疗法。
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[The role and regulation of EVI1 in normal hematopoiesis and hematopoietic malignancies].

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.

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