Non-immunoglobulin/BCL6 gene fusion in diffuse large B-cell lymphoma: prognostic implications

Abstract

3q27 translocation affecting the BCL6 gene is one of the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL). BCL6 translocation can involve not only one of the three immunoglobulin gene (Ig) loci but also another non-Ig chromosomal locus. 5'-rapid amplification of cDNA ends and long-distance inverse polymerase chain reaction (PCR) methods have identified a total of 13 recurrent non-Ig partner genes to date. As the result of non-Ig/BCL6 translocation, many types of regulatory sequences of each partner gene substitute for the 5' untranslated region of the BCL6 and the rearranged BCL6 is presumed to be under the control of the replaced promoter activity. BCL6 translocation occurs more frequently in extranodal DLBCL than in node-based disease. However, the impact of BCL6 translocation on the treatment outcome of DLBCL has been the subject of controversy. We found that survival of DLBCL patients with non-Ig partners was inferior to that of those with Ig/BCL6 translocation, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. We next created BCL6 expression plasmids containing a series of non-Ig/BCL6 fusion genes. COS-7 cells transiently transfected with these plasmids expressed high levels of Bcl-6 protein and showed characteristic punctate nuclear staining. These findings suggested that non-Ig/BCL6 translocation plays a pathogenetic role in a proportion of DLBCL.