Institute for Cancer Genetics and the Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA.
Curr Opin Hematol. 2013 Jul;20(4):336-44. doi: 10.1097/MOH.0b013e3283623d7f.
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 patient stratification based on molecular predictors and for the development of rational targeted therapies.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种侵袭性疾病，具有异质性的遗传、表型和临床特征。理解这种异质性的基础是在该疾病的管理方面取得进一步进展的关键步骤，而大约三分之一的患者仍然面临着临床挑战。这篇综述总结了目前关于 DLBCL 分子发病机制的知识，并描述了最近在该癌症的基因组特征描述方面的进展如何为其生物学提供了新的见解，揭示了一些潜在的诊断和治疗靶点。
在过去几年中，高分辨率技术的发展为识别遗传病变和/或信号通路中断提供了重要帮助，这些病变和/或信号通路中断对于 DLBCL 的起始和进展是必需的。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。这些通路的改变可能有利于表观遗传重编程和逃避细胞免疫。
鉴定导致 B 细胞恶性转化为 DLBCL 的遗传改变有助于更好地理解该疾病的生物学，并确定推动肿瘤进展或对治疗产生耐药性的关键节点。这些发现的快速发展有望根据分子预测因子对患者进行分层，并为开发合理的靶向治疗提供依据。
