The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma

摘要: Peripheral T-cell lymphomas (PTCLs) are generally aggressive non-Hodgkin with poor overall survival rates following standard therapy. One-third of PTCLs express interferon regulatory factor-4 (IRF4), a tightly regulated transcription factor involved in lymphocyte growth and differentiation. IRF4 drives tumor several lymphoid malignancies has been proposed as candidate therapeutic target. Because direct inhibitors not clinically available, we sought to characterize the mechanism by which expression is PTCLs. We demonstrated that constitutively expressed PTCL cells Myc proliferation. Using an inhibitor screen, identified nuclear κB (NF-κB) regulator cell then NF-κB subunits p52 RelB were transcriptional activators IRF4. Further analysis showed activation CD30 promotes activity subsequent expression. Finally, transcriptionally regulates Taken together, these data demonstrate novel positive feedback loop involving CD30, NF-κB, IRF4; further evidence for this was human tissue samples. Accordingly, may represent clinical means disrupt IRF4-positive