BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders.

Translocation t(14;19)(q32;q13) is a rare but recurrent abnormality in chronic lymphocytic leukemia and small cell lymphoma. It has been associated with rearrangements of the BCL3 gene, which is located at the breakpoint on chromosome 19 and is juxtaposed to the immunoglobulin heavy chain locus on chromosome 14 as a result of the translocation. This results in transcriptional up-regulation of the BCL3 gene, which encodes a transcription coactivator, an I-kappa B protein, probably contributing to disease progression. We found, among 4,487 cytogenetic analyses of lymphoproliferative disorders, six cases with a t(14;19)(q32;q13), five of which showed the classical t(14;19)(q32;q13) and one of which showed a three-way translocation t(7;19;14)(q21;q13;q32). The 14;19 translocation never occurred as a single abnormality; additional aberrations included trisomy 12 and several structural abnormalities. The cytogenetic examination was supplemented by molecular analysis using available probes for the BCL3 locus (p alpha 1.4P and p alpha 5B) in 1,150 of the 4,487 patients. Rearrangements of BCL3 could be detected in five cases, all of which had the classical t(14;19). In the case with t(7;19;14), the suspected BCL3 involvement could only be confirmed using long-range restriction mapping, indicating that, with the usually available BCL3 probes, rearrangements of this locus may be missed.