The genetic basis of diffuse large B-cell lymphoma.
The genetic basis of diffuse large B-cell lymphoma.
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DOI：
10.1097/moh.0b013e3283623d7f
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发表时间：
2013-07
影响因子：
3.2
通讯作者：
Pasqualucci L
中科院分区：
文献类型：
--
作者：
Pasqualucci L
弥漫性大 B 细胞淋巴瘤 (DLBCL) 是一种侵袭性疾病，具有异质性遗传、表型和临床特征。了解这种异质性的基础代表了该疾病治疗进一步进展的关键一步，该疾病对大约三分之一的患者来说仍然是一个临床挑战。这篇综述总结了目前关于 DLBCL 分子发病机制的知识，并描述了这种癌症基因组特征的最新进展如何为其生物学提供了新的见解，揭示了改进诊断和治疗的几个潜在靶点。在过去几年中，高分辨率技术的发展为识别 DLBCL 起始和进展所需的遗传病变和/或信号通路中断提供了重要帮助。这些研究揭示了以前未被认识到的细胞程序的参与，包括组蛋白/染色质重塑和免疫识别。这些途径的改变可能有利于表观遗传重编程并逃避细胞免疫。鉴定导致 B 细胞恶性转化为 DLBCL 的基因改变有助于更好地了解这种疾病的生物学特性，并确定驱动肿瘤进展或治疗耐药的关键节点。这些发现的快速发生将对基于分子预测因子的患者分层和合理靶向治疗的开发产生重大影响。
Diffuse large B cell lymphoma (DLBCL) is an aggressive disease featuring heterogeneous genetic, phenotypic and clinical characteristics. Understanding the basis for this heterogeneity represents a critical step toward further progress in the management of this disease, which remains a clinical challenge in approximately one third of patients. This review summarizes current knowledge about the molecular pathogenesis of DLBCL, and describes how recent advances in the genomic characterization of this cancer have provided new insights into its biology, revealing several potential targets for improved diagnosis and therapy. In the past few years, the development of high-resolution technologies has provided significant help in identifying genetic lesions and/or disrupted signaling pathways that are required for DLBCL initiation and progression. These studies uncovered the involvement of cellular programs that had not been previously appreciated, including histone/chromatin remodeling and immune recognition. Alterations in these pathways could favor epigenetic reprogramming and escape from cellular immunity. The identification of genetic alterations that contribute to the malignant transformation of a B cell into a DLBCL is helping to better understand the biology of this disease and to identify critical nodes driving tumor progression or resistance to therapy. The rapid pace at which these discoveries are taking place is poised to have significant impact for patients stratification based on molecular predictors and for the development of rational targeted therapies.