t(14;19)/BCL3 rearrangements in lymphoproliferative disorders: A review of 23 cases

The t(14;19)(q32.3;q13.2) is a rare but recurrent translocation found in patients with B-cell malignancies, mainly in chronic B-cell lymphoproliferative disorders. When occurring in chronic lymphocytic leukemia (CLL), atypical lymphocyte morphology and immunophenotype have been reported. A high proportion of patients with CLL and t(14;19) are aged less than 40 years. t(14;19) is often associated with rapidly progressive disease, and overall prognosis is poor compared to the expected survival in chronic lymphocytic leukemia and low-grade B-cell lymphoma. t(14;19) is rarely the sole cytogenetic aberration. Trisomy 12 is the most frequent associated abnormality, and is observed in 50% of cases. t(14;19) involves the BCL3 gene, which is located at the breakpoint on chromosome 19 and is juxtaposed to the immunoglobulin heavy chain gene locus on chromosome 14 (often in the switch α region) in a “head-to-head” configuration. The translocation does not interrupt the transcriptional integrity of BCL3, but is associated with overexpression of this gene, which encodes an IϰB-like protein and modulates the activity of the NF-ϰB transcription factors. The genes affected by overexpression of BCL3 remain to be identified.