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淋巴恶性肿瘤中异常的表观遗传基因调控。

Aberrant epigenetic gene regulation in lymphoid malignancies.

机构信息

Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212, USA.

出版信息

Semin Hematol. 2013 Jan;50(1):38-47. doi: 10.1053/j.seminhematol.2013.01.003.

Abstract

In lymphoid malignancies, aberrant epigenetic mechanisms such as DNA methylation and histone modifications influence chromatin architecture and can result in altered gene expression. These alterations commonly affect genes that play important roles in the cell cycle, apoptosis, and DNA repair in non-Hodgkin lymphoma (NHL). The ability to identify epigenetic modifications to these important genes has increased exponentially due to advances in technology. As a result, there are well-defined, gene-specific epigenetic aberrations associated with NHL comprising follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and diffuse large B-cell lymphoma (DLBCL). The identification of these genes is important because they may be used as biomarkers for prognosis, diagnosis and in developing improved treatment strategies. Also important, in the control of gene expression, is the packaging of DNA within the nucleus of a cell. This packaging can be distorted by epigenetic alterations and may alter the accessibility of certain regions of the genome in cancer cells. This review discusses the impact of known epigenetic aberration on the regulation of gene expression in NHL and provides insight into the spatial conformation of the genome (DNA packaging) in acute lymphoblastic leukemia.

摘要

在淋巴恶性肿瘤中,异常的表观遗传机制,如 DNA 甲基化和组蛋白修饰,会影响染色质结构,并导致基因表达的改变。这些改变通常会影响细胞周期、细胞凋亡和非霍奇金淋巴瘤 (NHL) 中 DNA 修复的重要基因。由于技术的进步,能够识别这些重要基因的表观遗传修饰呈指数级增长。因此,与 NHL 相关的、具有明确特征的基因特异性表观遗传异常包括滤泡性淋巴瘤 (FL)、套细胞淋巴瘤 (MCL)、慢性淋巴细胞白血病 (CLL) 和弥漫性大 B 细胞淋巴瘤 (DLBCL)。这些基因的鉴定很重要,因为它们可以用作预后、诊断和开发改进治疗策略的生物标志物。同样重要的是,在基因表达的调控中,DNA 在细胞核内的包装方式。这种包装可能会被表观遗传改变扭曲,并可能改变癌细胞中基因组的某些区域的可及性。本文讨论了已知的表观遗传异常对 NHL 中基因表达调控的影响,并深入了解了急性淋巴细胞白血病中基因组的空间构象(DNA 包装)。

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