Scheeren Ferenc A, Diehl Sean A, Smit Laura A, Beaumont Tim, Naspetti Marianne, Bende Richard J, Blom Bianca, Karube Kennosuke, Ohshima Koichi, van Noesel Carel J M, Spits Hergen
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Blood. 2008 May 1;111(9):4706-15. doi: 10.1182/blood-2007-08-105643. Epub 2008 Feb 22.
Classical Hodgkin lymphoma (HL) is a malignant disorder characterized by the presence of neoplastic mononucleated Hodgkin and multinucleated Reed-Sternberg cells. Here, we show that both the interleukin (IL)-21 receptor as well as IL-21 are expressed by HL cells. IL-21 activates signal transducer of activation and transcription 3 (STAT3) and STAT5 in HL cell lines and activated human B cells. Ectopic expression of constitutively active STAT5 in primary human B cells resulted in immortalized B cells that have lost the B-cell phenotype and strongly resembled HL cells, which could partially be rescued by ectopic expression of the B cell-determining transcription factor E47. Data from experiments using reporter assays and overexpression of constitutively active IKK2 support the hypothesis that the STAT5 and nuclear factor-kappaB (NF-kappaB) pathways collaborate in HL genesis.
经典型霍奇金淋巴瘤（HL）是一种恶性疾病，其特征是存在肿瘤性单核霍奇金细胞和多核里德-斯腾伯格细胞。在此，我们表明HL细胞同时表达白细胞介素（IL）-21受体和IL-21。IL-21在HL细胞系和活化的人B细胞中激活信号转导子和转录激活子3（STAT3）以及STAT5。在原代人B细胞中组成型活性STAT5的异位表达导致永生化B细胞，这些细胞已丧失B细胞表型，且与HL细胞极为相似，通过B细胞决定性转录因子E47的异位表达可部分挽救这一现象。使用报告基因检测和组成型活性IKK2过表达的实验数据支持STAT5和核因子-κB（NF-κB）通路在HL发生过程中协同作用的假说。
