IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis

FA Scheeren, SA Diehl, LA Smit… - Blood, The Journal …, 2008 - ashpublications.org
FA Scheeren, SA Diehl, LA Smit, T Beaumont, M Naspetti, RJ Bende, B Blom, K Karube
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
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 …
Abstract
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-κB (NF-κB) pathways colaborate in HL genesis.
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