Pathogenetic and Clinical Implications of Non- Immunoglobulin; BCL6 Translocations in B-Cell Non-Hodgkin's Lymphoma

Chromosomal translocations affecting band 3q27, where BCL6 gene is located, are among the most common genetic abnormalities in non-Hodgkin's lymphoma of B-cell type (B-NHL). The BCL6 gene encodes a BTB/POZ zinc finger transcription factor, which exerts repressive activity by recruiting corepressor molecules. The 3q27/BCL6 translocation is unique in that it can involve not only immunoglobulin (Ig) genes but also non-Ig chromosomal loci as a partner. To date, around 20 non-Ig partner genes have been identified. As a result of non-Ig; BCL6 translocations, many types of regulatory sequences of each partner gene substitute for the 5' untranslated region of BCL6, and the rearranged BCL6 comes under the control of the replaced promoter. The introduction of non-Ig; BCL6 constructs into transformed cells led to high-level Bcl-6 protein expression in the nucleus, while BCL6 mRNA levels in clinical materials of diffuse large B-cell lymphoma (DLBCL) with non-Ig; BCL6 translocations were unexpectedly low. A comparative study suggested that non-Ig; BCL6 translocation and a low level of BCL6 mRNA expression are concordant indicators of a poor clinical outcome in cases of DLBCL. The coexistence of a non-Ig; BCL6 translocation with t (14; 18)(q32; q21) in a single clone did not significantly affect the clinical features of follicular lymphoma. The pathogenetic and clinical implications of non-Ig; BCL6 translocations in B-NHL subtypes may not be identical to those of Ig; BCL6.