Korać Petra, Dotlić Snježana, Matulić Maja, Zajc Petranović Matea, Dominis Mara
Department of Biology, Division of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia.
Department of Pathology and Cytology, University Hospital Center Zagreb, 10000 Zagreb, Croatia.
Genes (Basel). 2017 Apr 4;8(4):115. doi: 10.3390/genes8040115.
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.
B细胞淋巴瘤主要起源于次级淋巴组织生发中心B细胞的不同发育阶段。有许多信号通路影响B细胞淋巴瘤发生的起始和发展。代表信号网络分支点的几种关键蛋白的功能因异常表达、降解和/或积累而发生改变，这些事件决定了受影响B细胞的命运。最具影响力的转录因子之一是核磷蛋白MYC，它通常与B细胞淋巴瘤患者的不良预后相关。在B细胞淋巴瘤发生过程中，致癌性MYC变体通过各种机制失调，如基因易位、基因扩增及其表达的表观遗传失调。由于下游信号级联的改变，过表达MYC的肿瘤性B细胞迅速增殖，避免凋亡，并对大多数传统治疗无反应。本综述将总结MYC在B细胞发育和肿瘤发生中的作用，以及其对当前B细胞淋巴瘤分类的意义。我们比较了受过表达MYC影响的不同淋巴瘤中转化B细胞内的通讯网络，并对不同患者群体中MYC与肿瘤预后的关联进行了荟萃分析。
