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This project investigates the molecular mechanisms underlying the development of activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL), an aggressive human lymphoma subtype characterized by poor patient outcome. Currently, only 50% of patients can be cured following a combined treatment with the B-cell depleting anti-CD20 antibody rituximab and the CHOP chemotherapy regimen (R-CHOP), underlining the need for improved therapeutic strategies. ABC DLBCLs are characterized by distinct transcriptional alterations; a better understanding of these is a prerequisite to develop novel therapeutic strategies. Here, we propose to elucidate the contribution of selected transcription factors to the molecular pathogenesis of this entity in a collaborative manner, using combined biochemical and genetic approaches. These synergistic approaches will unravel novel pathways and genes that specifically drive the development of ABC DLBCL and thereby lead to a significantly better understanding of the biology of ABC DLBCL. Moreover, they might identify novel therapeutic targets and generate diagnostic tools.