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Role of MYC in B Cell Lymphomagenesis

机译:MYC在B细胞淋巴瘤发生中的作用

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B cell lymphomas mainly arise from different developmental stages of B cells in germinal centers of secondary lymphoid tissue. There are a number of signaling pathways that affect the initiation and development of B cell lymphomagenesis. The functions of several key proteins that represent branching points of signaling networks are changed because of their aberrant expression, degradation, and/or accumulation, and those events determine the fate of the affected B cells. One of the most influential transcription factors, commonly associated with unfavorable prognosis for patients with B cell lymphoma, is nuclear phosphoprotein MYC. During B cell lymphomagenesis, oncogenic MYC variant is deregulated through various mechanisms, such as gene translocation, gene amplification, and epigenetic deregulation of its expression. Owing to alterations of downstream signaling cascades, MYC-overexpressing neoplastic B cells proliferate rapidly, avoid apoptosis, and become unresponsive to most conventional treatments. This review will summarize the roles of MYC in B cell development and oncogenesis, as well as its significance for current B cell lymphoma classification. We compared communication networks within transformed B cells in different lymphomas affected by overexpressed MYC and conducted a meta-analysis concerning the association of MYC with tumor prognosis in different patient populations.
机译:B细胞淋巴瘤主要来自次级淋巴组织生发中心中B细胞的不同发育阶段。有许多信号通路影响B细胞淋巴瘤的发生和发展。代表信号网络分支点的几种关键蛋白的功能因其异常的表达,降解和/或积累而发生了变化,这些事件决定了受影响的B细胞的命运。通常与B细胞淋巴瘤患者预后不良有关的最具影响力的转录因子之一是核磷蛋白MYC。在B细胞淋巴瘤的形成过程中,致癌MYC变体通过多种机制失控,例如基因易位,基因扩增和其表达的表观遗传失调。由于下游信号传导级联的改变,过表达MYC的赘生性B细胞迅速增殖,避免凋亡,并且对大多数常规治疗无反应。这篇综述将总结MYC在B细胞发育和肿瘤发生中的作用,及其对当前B细胞淋巴瘤分类的意义。我们比较了在过度表达MYC影响的不同淋巴瘤中转化B细胞内的通讯网络,并进行了关于MYC与不同患者人群中肿瘤预后的关联的荟萃分析。

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