Specific peptide disruption of the BCL6 repression complex reveals its trasncriptional mechanism of action in normal and malignant B-cells and is a novel therapeutic approach for Diffuse Large B-Cell Lymphoma.

POLO, JM; DELL´OSO, T; RANUNCOLO, SM; KIAN, CL; PRIVÉ, G; LICHT, J; MELNICK, AM

San Diego, California.

Congreso; 46th Annual Meeting of the American Society of Hematology; 2004

American Society of Hematology

The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional and biological properties, we generated a peptide that specifically binds BCL6 and blocks corepressor recruitment in vivo. This inhibitor disrupts BCL6-mediated repression and establishment of silenced chromatin, reactivates natural BCL6 target genes, and abrogates BCL6 biological function in B cells. In BCL6-positive lymphoma cells, peptide blockade caused apoptosis and cell cycle arrest. BTB domain peptide inhibitors may constitute a novel therapeutic agent for B-cell lymphomas.