文章：

霍奇金淋巴瘤的生物学

The biology of Hodgkin's lymphoma

原文发布日期：2008-12-11

DOI: 10.1038/nrc2542

类型: Review Article

开放获取: 否

要点：

1. Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin's lymphoma are probably derived from germinal centre B cells that have acquired disadvantageous immunoglobulin variable chain gene mutations and normally would have undergone apoptosis, whereas lymphocytic and histiocytic (L&H) cells of NLPHL appear to derive from antigen-selected germinal centre B cells. Few cases of classical Hodgkin's lymphoma originate from T cells.
2. Classical Hodgkin's lymphoma is unique among human lymphomas in the extent to which the lymphoma cells have undergone reprogramming of gene expression. They have lost expression of most B cell-typical genes and acquired expression of multiple genes that are typical for other types of cells of the immune system.
3. Multiple signalling pathways and transcription factors show deregulated activity in HRS cells, including nuclear factor-κB, Jak–Stat, PI3K–Akt, Erk, AP1, notch 1 and receptor tyrosine kinases.
4. The transforming events involved in the generation of HRS cells are only partly understood, but several known recurrent genetic lesions involve members of the nuclear factor-κB or Jak–Stat signalling pathways.
5. HRS cells attract many cells into the lymphoma tissue, resulting in a typical inflammatory microenvironment. This environment probably promotes the survival of HRS cells and helps them to escape attack from cytotoxic T or natural killer cells.

要点翻译：

1. 经典霍奇金淋巴瘤的霍奇金与里德-斯特恩伯格细胞很可能源自生发中心B细胞——这些细胞获得了不利的免疫球蛋白可变区基因突变，正常情况下本应发生凋亡；而结节性淋巴细胞为主型霍奇金淋巴瘤的淋巴细胞与组织细胞则似乎来源于抗原选择的生发中心B细胞。少数经典霍奇金淋巴瘤病例起源于T细胞。
2. 经典霍奇金淋巴瘤在基因表达重编程的程度上是人类淋巴瘤中的独特存在。瘤细胞失去了大多数B细胞典型基因的表达，并获得了免疫系统其他细胞类型的多种典型基因表达。
3. 霍奇金与里德-斯特恩伯格细胞中存在多条信号通路和转录因子活性失调，包括核因子κB、Jak–Stat、PI3K–Akt、Erk、AP1、Notch 1及受体酪氨酸激酶。
4. 关于霍奇金与里德-斯特恩伯格细胞转化过程中的分子事件目前仅部分明确，但已知的若干复现性遗传异常涉及核因子κB或Jak–Stat信号通路成员。
5. 霍奇金与里德-斯特恩伯格细胞能吸引大量细胞聚集于淋巴瘤组织，形成典型的炎症微环境。这种环境很可能促进霍奇金与里德-斯特恩伯格细胞的存活，并帮助其逃避免疫系统中细胞毒性T细胞或自然杀伤细胞的攻击。

英文摘要：

Hodgkin's lymphoma was first described in 1832. The aetiology of this lymphoma, however, remained enigmatic for a long time. Only within the past 10 years has the B-cell nature of the pathognomonic Hodgkin and Reed–Sternberg (HRS) cells been revealed, along with several recurrent genetic lesions. The pathogenetic role for Epstein–Barr virus infection has also been substantiated. HRS cells in classical Hodgkin's lymphoma have several characteristics that are unusual for lymphoid tumour cells, and the Hodgkin's lymphoma microenvironment is dominated by an extensive mixed, potentially inflammatory cellular infiltrate. Understanding the contribution of all of these changes to the pathogenesis of this disease is essential for the development of novel therapies.

摘要翻译： 

霍奇金淋巴瘤最早于1832年被描述。然而，其病因长期以来一直难以捉摸。仅在过去的10年中，才揭示了标志性的霍奇金和Reed-Sternberg（HRS）细胞的B细胞本质，以及若干复发性遗传损伤。爱泼斯坦-巴尔病毒感染的发病作用也得到了证实。经典霍奇金淋巴瘤中的HRS细胞具有一些对于淋巴细胞肿瘤细胞而言不寻常的特征，且霍奇金淋巴瘤的微环境以大量混合的、潜在炎症性的细胞浸润为主。理解所有这些变化对该疾病发病机制的贡献，对于开发新型疗法至关重要。

原文链接：

The biology of Hodgkin's lymphoma