IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis.
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.
Scheeren
Ferenc A
FA
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Diehl
Sean A
SA
Smit
Laura A
LA
Beaumont
Tim
T
Naspetti
Marianne
M
Bende
Richard J
RJ
Blom
Bianca
B
Karube
Kennosuke
K
Ohshima
Koichi
K
van Noesel
Carel J M
CJ
Spits
Hergen
H
D001402:B-Lymphocytes; D006689:Hodgkin Disease / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000032:analysis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D009363:Neoplasm Proteins; D053655:Receptors, Interleukin-21 / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D000098546:Interleukin-21
D007378:Interleukins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D053655:Receptors, Interleukin-21; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D000098546:Interleukin-21