The role of BCL6 in lymphomas and routes to therapy
Simon D. Wagner,
Matthew Ahearne,
Paul Ko Ferrigno,
Simon D. Wagner
Department of Cancer Studies and Molecular Medicine and MRC Toxicology Unit, University of Leicester, Leicester, UK
Search for more papers by this authorMatthew Ahearne
Department of Cancer Studies and Molecular Medicine and MRC Toxicology Unit, University of Leicester, Leicester, UK
Search for more papers by this authorPaul Ko Ferrigno
Section of Experimental Therapeutics, Leeds Institute of Molecular Medicine, University of Leeds and St James’s University Hospital, Leeds, UK
Search for more papers by this authorSimon D. Wagner,
Matthew Ahearne,
Paul Ko Ferrigno,
Simon D. Wagner
Department of Cancer Studies and Molecular Medicine and MRC Toxicology Unit, University of Leicester, Leicester, UK
Search for more papers by this authorMatthew Ahearne
Department of Cancer Studies and Molecular Medicine and MRC Toxicology Unit, University of Leicester, Leicester, UK
Search for more papers by this authorPaul Ko Ferrigno
Section of Experimental Therapeutics, Leeds Institute of Molecular Medicine, University of Leeds and St James’s University Hospital, Leeds, UK
Search for more papers by this authorDr Simon Wagner, MRC Toxicology Unit, Hodgkin Building, University of Leicester, Room 323, Lancaster Road, Leicester LE1 9HN, UK. E-mail: [email protected]
Summary
BCL6 is a transcription factor that has essential B-cell and T-cell roles in normal antibody responses. It is involved in chromosomal translocations in diffuse large B-cell lymphoma (DBCL; including primary mediastinal B-cell lymphoma) and nodular lymphocyte predominant Hodgkin lymphoma, and is expressed in follicular lymphoma and Burkitt's lymphoma. The neoplastic T-cells of angioimmunoblastic T-cell lymphoma also express BCL6. BCL6 prevents terminal B-cell differentiation largely through repression of PRDM1. In the “cell of origin” classification of DLBCL BCL6 is associated with the germinal centre subtype, which carries a good response to modern treatments. More recently, specific BCL6 antagonists, including small molecule inhibitors, have been developed. These antagonists have demonstrated that DLBCL cells, in which BCL6 is transcriptionally active, are dependent on this gene for survival. BCL6 antagonists are active against primary DLBCL and may find future application in the treatment of lymphomas.
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