Constitutive activation of STAT proteins in the HDLM-2 and L540 Hodgkin lymphoma-derived cell lines supports cell survival.

Survival and proliferation of Hodgkin lymphoma (HL) cells are influenced by many cytokines produced by different cell types in the lymph node microenvironment. STAT, family of transcription factors, are key mediators of cytokine signaling and their perturbation contributes to various human diseases. Electrophoretic mobility shift and phosphoprotein immunoblotting analyses were used to study STAT activation in HL cell lines. We thus observed high levels of constitutively activated STAT1, 3, 5 and 6 in HDLM-2 and L540 cells, which could be correlated with JAK kinase activation. In contrast KM-H2 cells did not display STAT activation. Preventing constitutive STAT activation by specific JAK kinases inhibitors induced apoptosis of HL cell lines and was associated with a strong decrease in the expression of the anti-apoptotic genes IAP-1, IAP-2, Bcl-xL, Bfl1 and Traf1. Silencing of JAKs by specific siRNAs also induced apoptosis of HL cells. Altogether, these results suggest that aberrant STAT activation in Hodgkin cells may promote cell survival and as a consequence facilitate oncogenic transformation.