Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, 13353 Berlin, Germany.
Curr Mol Med. 2011 Apr;11(3):236-45. doi: 10.2174/156652411795243423.
Classical Hodgkin lymphoma (cHL) is now recognized as a B-cell-derived lymphoma which is characterized by only about 1% malignant pathognomonic Hodgkin and Reed-Sternberg (HRS) cells and an abundant infiltrate of reactive bystander cells. HRS cells are unique with respect to their lost B-cell-specific gene expression pattern and recurrent genetic lesions. Aberrant activity of Notch signaling, a highly conserved developmental pathway, acts as a negative regulator of the B cell program in HRS cells and thereby contributes to their reprogramming. Another striking feature and the major pathogenetic mechanism in HRS cells is constitutive NF-κB activation. A number of aberrations that contribute to canonical NF-κB activity in HRS cells have been described such as genetic lesions, deregulated receptor signaling and Epstein-Barr virus (EBV) infection. The importance of Notch and NF-κB signaling for cHL pathogenesis, their potential cross-talk and implications for future therapeutic applications are being discussed.
经典型霍奇金淋巴瘤（cHL）现在被认为是一种 B 细胞来源的淋巴瘤，其特征仅为约 1%恶性的特征性霍奇金和里德-斯特恩伯格（HRS）细胞，以及丰富的反应性旁观者细胞浸润。HRS 细胞在其丢失的 B 细胞特异性基因表达模式和反复发生的遗传病变方面是独特的。 Notch 信号通路的异常活性是一种高度保守的发育途径，作为 HRS 细胞中 B 细胞程序的负调节剂，从而有助于其重编程。另一个显著特征和 HRS 细胞中的主要发病机制是组成型 NF-κB 激活。已经描述了许多导致 HRS 细胞中典型 NF-κB 活性的异常，例如遗传病变、受体信号失调和 Epstein-Barr 病毒（EBV）感染。 Notch 和 NF-κB 信号通路对 cHL 发病机制的重要性、它们的潜在串扰以及对未来治疗应用的影响正在讨论中。
