FOXP1 in ABC DLBCL

High expression of the FOXP1 transcription factor distinguishes the highly aggressive Activated B Cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL) from the more indolent Germinal Center (GCB) DLBCL subtype and is correlated with poor prognosis. A genetic or functional role for FOXP1 in lymphomagenesis and/or tumor maintenance, however, remains unknown. Here, we report that sustained expression of FOXP1 is necessary for ABC DLBCL cell line survival. Genome-wide transcript profiling reveals that FOXP1 acts directly and indirectly by enforcing expression of known ABC DLBCL hallmarks, including the classical NF-kappaB survival pathway. Our data further suggest that FOXP1 maintains the ABC subtype distinction by repressing gene expression programs dominant in GCB DLBCL and supports a model in which the target of ABC DLBCL transformation is a transitory cell type en route from the germinal center B cell to the terminally differentiated plasma cell. HBL1 (n=12) or TMD8 (n=12) cells were infected with either a Ctrl shRNA or with shRNAs targeting FOXP1. The shRNA expression was induced for 1, 2, 3, or 4 days.