DLBCL is the most frequent and aggressive form of non-Hodgkin's lymphoma. The still high percentage of mortality is in part due to the heterogeneity of DLBCL at genetic level. Among genetic alterations, a recurrent gain at 11q24.3 was detected in 26% of DLBCL. It was associated with higher expression of ETS1 and FLI1 transcription factors. Silencing of both genes led to cell death and a block in proliferation in a DLBCL cell line bearing the specific 11q gain but only FLI1 silencing gave a similar phenotype in cell lines without the gain. At molecular level, ETS1 directly and negatively regulates BLIMP1 expression. Importantly, ETS1 or FLI1 silencing leads to changes in the expression of B cell important genes. This project reveals ETS1 and FLI1 as interesting drug targets to be further analyzed. In addition, the status of MYC gene was analyzed in this cohort of DLBCL patients treated with R-CHOP.