髓系肿瘤中的单倍体转录因子。

IF 28.4 1区 医学 Q1 PATHOLOGY
Tanner C Martinez, Megan E McNerney
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引用次数: 0

摘要

许多转录因子(TF)作为具有杂合表型的肿瘤抑制基因发挥作用,但单倍性不足在肿瘤形成中的作用通常被低估。骨髓细胞也是如此,它们通常由一个微妙平衡和相互连接的转录网络调节。对TF在该回路中的剂量的详细了解为白血病转录组提供了线索。在这篇综述中,我们讨论了单倍充足转录因子(HITF)的新特点。我们假设:(a)单等位基因和双等位基因缺失可能具有不同的细胞结果;(b) TF的活性存在于比传统孟德尔遗传剂量更大的范围内;和(c)TF如何被删除或突变影响细胞表型。HITF的净作用是髓系分化阻滞和髓系肿瘤过程中细胞间异质性增加。《病理学年度评论:疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Haploinsufficient Transcription Factors in Myeloid Neoplasms.

Many transcription factors (TFs) function as tumor suppressor genes with heterozygous phenotypes, yet haploinsufficiency generally has an underappreciated role in neoplasia. This is no less true in myeloid cells, which are normally regulated by a delicately balanced and interconnected transcriptional network. Detailed understanding of TF dose in this circuitry sheds light on the leukemic transcriptome. In this review, we discuss the emerging features of haploinsufficient transcription factors (HITFs). We posit that: (a) monoallelic and biallelic losses can have distinct cellular outcomes; (b) the activity of a TF exists in a greater range than the traditional Mendelian genetic doses; and (c) how a TF is deleted or mutated impacts the cellular phenotype. The net effect of a HITF is a myeloid differentiation block and increased intercellular heterogeneity in the course of myeloid neoplasia.

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来源期刊
CiteScore
62.60
自引率
0.00%
发文量
40
期刊介绍: The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.
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