MYC Alterations in Diffuse Large B-Cell Lymphomas
MYC Alterations in Diffuse Large B-Cell Lymphomas
复制标题
DOI：
10.1053/j.seminhematol.2015.01.009
复制
发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Campo, Elias
中科院分区：
文献类型：
--
作者：
Karube, Kennosuke;Campo, Elias
MYC是一种与许多生理功能相关的转录因子，包括细胞凋亡和强致癌潜能。MYC的表达在正常淋巴样细胞中受到严格调控，在继发性淋巴滤泡形成的初始阶段和生发中心光区的一部分中心细胞中表达水平较高。BCL6和BLIMP1分别抑制正常生发中心B和浆细胞中MYC的表达。矛盾的是，大多数MYC遗传改变的淋巴瘤起源于通常不表达MYC的细胞，这表明这些肿瘤需要发生额外的致癌事件来克服MYC调节机制及其促凋亡功能。MYC重排和较小程度的基因扩增在约5%至14%的弥漫性大b细胞淋巴瘤（DLBCL）中被检测到，这些改变通常与BCL2或BCL6重排有关。这些改变的同时存在使肿瘤具有更强的侵袭性，患者的预后较差。BCL2和MYC蛋白也可能在DLBCL中独立于基因改变而共表达，这种双重表达也会导致预后不良，尽管不像双重基因命中那样令人沮丧。其他因素可能调节双重打击病变的生物学效应，因为MYC易位到非igh伴侣或MYC和BCL2蛋白表达水平较低的肿瘤可能具有较低的侵袭性行为。需要进一步的研究来确定DLBCL中MYC畸变的临床意义，并确定最合适的诊断策略来识别这些肿瘤。(C) 2015爱思唯尔公司版权所有。
MYC is a transcription factor associated with numerous physiological functions, including apoptosis, and strong oncogenic potential. MYC expression is tightly regulated in normal lymphoid cells with high levels in the initial steps of the secondary lymphoid follicle formation and in a subset of centrocytes of the germinal center light zone. BCL6 and BLIMP1 repress MYC expression in normal germinal center B and plasma cells, respectively. Paradoxically, most lymphomas with MYC genetic alterations originate from cells that usually do not express MYC, suggesting that these tumors need to develop additional oncogenic events to overcome the MYC regulatory mechanisms and also its proapoptotic function. MYC rearrangements, and to a lesser extent gene amplifications, have been detected in approximately 5% to 14% of diffuse large B-cell lymphoma (DLBCL) and these alterations are frequently associated with BCL2 or BCL6 rearrangements. The concurrent presence of these alterations confers a more aggressive behavior to the tumors with poor outcome of the patients. BCL2 and MYC protein may also be coexpressed in DLBCL independently of gene alterations and this double expression also confers poor prognosis, although not as dismal as that of double genetic hits. Additional factors may modulate the biological effect of the double hit lesions because tumors in which MYC is translocated to non-IGH partner or MYC and BCL2 protein that are expressed at lower levels may have a less aggressive behavior. Further studies are needed to define the clinical implications of MYC aberrations in DLBCL and determine the most appropriate diagnostic strategy to identify these tumors. (C) 2015 Elsevier Inc. All rights reserved.