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对 MYC 诱导的淋巴瘤发生机制的认识进展。

Advances in the understanding of MYC-induced lymphomagenesis.

机构信息

Institute of Physiological Chemistry, University of Ulm, Ulm, Germany.

出版信息

Br J Haematol. 2010 May;149(4):484-97. doi: 10.1111/j.1365-2141.2010.08159.x. Epub 2010 Mar 21.

Abstract

Up to 70% of all human malignancies show elevated expression of MYC. MYC is a pleiotropic transcription factor involved in many aspects of cellular development and physiology. Besides direct regulation of target genes involved in proliferation and growth MYC is implicated in controlling the complex networks of microRNAs and apoptosis mediators. The mode of MYC deregulation varies between different tumor entities. In most types of cancer high MYC levels are secondary to alterations in cell signalling pathways, leading to enhanced proliferation of the transformed cells. In some haematological malignancies, like Burkitt lymphoma (BL) and subsets of diffuse large B-cell lymphomas, elevated MYC levels are a direct consequence of genomic aberrations involving the MYC locus. BL is considered the prime example for MYC-induced lymphomagenesis. In comparison to other haematological malignancies it has the highest MYC-expression and is often connected to Epstein-Barr virus (EBV) infection. Over the past five decades BL has provided an invaluable tool for the entire discipline of oncology, helping to decipher many aspects of tumor biology. This review summarizes recent advances in the research on MYC-induced lymphomagenesis, focusing on the regulation of microRNAs and apoptosis, and possible contributions of EBV for lymphoma development.

摘要

高达 70%的人类恶性肿瘤表现出 MYC 的高表达。MYC 是一种多功能转录因子,参与细胞发育和生理的许多方面。除了直接调节参与增殖和生长的靶基因外,MYC 还参与控制 miRNA 和凋亡介质的复杂网络。MYC 失调的模式在不同的肿瘤实体之间有所不同。在大多数类型的癌症中,高 MYC 水平是细胞信号通路改变的结果,导致转化细胞的增殖增强。在一些血液恶性肿瘤中,如伯基特淋巴瘤(BL)和弥漫性大 B 细胞淋巴瘤的某些亚型,MYC 水平的升高是涉及 MYC 基因座的基因组异常的直接结果。BL 被认为是 MYC 诱导的淋巴瘤发生的典型例子。与其他血液恶性肿瘤相比,它的 MYC 表达最高,通常与 Epstein-Barr 病毒(EBV)感染有关。在过去的五十年中,BL 为肿瘤学的整个学科提供了一个非常宝贵的工具,有助于阐明肿瘤生物学的许多方面。这篇综述总结了 MYC 诱导的淋巴瘤发生的研究进展,重点关注 miRNA 和凋亡的调控,以及 EBV 对淋巴瘤发展的可能贡献。

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