Asano Naoko
Department of Molecular Diagnostics, Nagano Prefectural Suzaka Hospital.
Rinsho Ketsueki. 2015 Oct;56(10):2024-31. doi: 10.11406/rinketsu.56.2024.
In 1832, Dr. Thomas Hodgkin reported the first cases with this malignancy, which came to be named Hodgkin's disease. The cells that are a hallmark of this disease, Hodgkin and Reed-Sternberg (HRS) cells, account for only 1% of those in tumor tissues, with the majority of cells in Hodgkin lymphoma being of various inflammatory types. Advances in molecular techniques have contributed to molecular biological analysis of HRS cells. Intriguingly, HRS cells are derived from germinal center B-cells, but have lost their B-cell gene-expression and co-express non-B-cell genes. Multiple signaling pathways, including the NFκB and JAK/STAT pathways, show deregulated activity in HRS cells, suggesting an important role for these pathways in the pathogenesis of Hodgkin lymphoma. This article describes the molecular pathological characteristics of HRS cells: 1) the cellular origin of HRS cells, 2) deregulated gene expression in HRS cells, 3) genetic alterations and 4) epigenetic alterations in HRS cells, 5) the lost B-cell phenotype of HRS cells, 6) the role of EBV in Hodgkin lymphoma pathogenesis, and 7) micro-environmental interactions between HRS and reactive cells.
1832年，托马斯·霍奇金医生报告了首例这种恶性肿瘤病例，该病后来被命名为霍奇金病。作为这种疾病标志的细胞，即霍奇金和里德-斯腾伯格（HRS）细胞，在肿瘤组织细胞中仅占1%，霍奇金淋巴瘤中的大多数细胞属于各种炎症类型。分子技术的进步推动了对HRS细胞的分子生物学分析。有趣的是，HRS细胞起源于生发中心B细胞，但已失去其B细胞基因表达并共表达非B细胞基因。包括NFκB和JAK/STAT途径在内的多种信号通路在HRS细胞中显示出失调的活性，表明这些途径在霍奇金淋巴瘤发病机制中起重要作用。本文描述了HRS细胞的分子病理特征：1）HRS细胞的细胞起源，2）HRS细胞中失调的基因表达，3）HRS细胞中的基因改变和4）表观遗传改变，5）HRS细胞丧失的B细胞表型，6）EBV在霍奇金淋巴瘤发病机制中的作用，以及7）HRS细胞与反应性细胞之间的微环境相互作用。
