Identification of a transcriptional unit adjacent to the breakpoint in the 14;19 translocation of chronic lymphocytic leukemia

Abstract

The t(14;19)(q32.3;q13.1) is a recurring translocation found in the neoplastic cells of some patients with chronic lymphocytic leukemia (CLL). We have previously cloned the translocation breakpoint junction present in the leukemic cells from one such patient. In the present study, we have cloned and sequenced the breakpoint junction from a second patient. The breakpoint on chromosome 14 occurs within a switch region upstream of the immunoglobulin heavy chain C alpha 1 sequence. We detected a 2.1-2.3 kb transcript on Northern blots using a probe from chromosome 19 adjacent to this breakpoint. S1 nuclease protection experiments showed that transcription of the gene proceeds in a direction away from the breakpoint junction. This gene (for which we propose the name BCL3) may contribute to the malignant development of B-lymphocytes following the chromosome translocation. If so, it is the first protooncogene identified whose activation is principally associated with CLL.