"FOXP1 (Forkhead box-P1) is a winged-helix transcription factor that has been demonstrated to be expressed in a subset of activated B-cell type (ABC) diffuse B-cell lymphomas (DLBCLs). Strong FOXP1 expression appears to have an additive adverse role in the pathogenesis and clinical behavior of ABC-DLBCL. We believe that a better understanding of the molecular impact of FOXP1 deregulation in DLBCL will help us to improve the correct stratification of cancer patients as a prerequisite for acute diagnosis, and will allow us to propose novel pre-clinical therapeutic strategies to target the FOXP1-axis. To achieve this, we propose to characterize a collection of primary human DLBCL samples, stablished cell lines and the novel Emu-FOXP1 transgenic mouse model that has been recently generated in our lab, in an attempt to identify deregulated B-cell functional pathways, as well as sets of genetic and epigenetic events that might be ""passengers"" and/or ""drivers"" of lymphomagenesis. Our preliminary data has identified the B-cell mutagenic enzyme AID (activation-induced deaminase) as a FOXP1-target gene that could promote genetic and epigenetic instability in germinal-center B-cells. Consequently, we propose to explore the functional interaction of FOXP1 and AID both during normal B-cell activation and malignant B-cell transformation. By exploring functional and therapeutic strategies of targeting potential FOXP1/AID-related targets we pursue the development of translational protocols that could be used in the clinic to better diagnose patients with DLBCL and set the basis for designing future treatments and clinical trials."
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