Juxtaposition of human bcl-2 and immunoglobulin lambda light chain gene in chronic lymphocytic leukemia is the result of a reciprocal chromosome translocation between chromosome 18 and 22

Abstract

The human bcl-2 gene is a oncogene candidate which is involved in the t(14;18) translocation specifically associated with follicular and diffuse B cell lymphomas. This translocation deregulates bcl-2 gene expression by placing it into immunoglobulin heavy chain locus (IgH). We have recently reported a case of chronic lymphocytic leukemia (CLL 1446) carrying a unique bcl-2 gene rearrangement with the immunoglobulin lambda light chain (Ig lambda) gene. This juxtaposition of the bcl-2 and Ig lambda genes resembles a variant chromosome translocation in Burkitt's lymphoma, although karyotype data of CLL 1446 is not available. In this paper, we completed the structural analysis of the bcl-2/Ig lambda gene rearrangement in CLL 1446 by cloning the corresponding partner of the rearrangement. This revealed that the juxtaposition of the bcl-2 and Ig lambda genes is a result of a reciprocal chromosome translocation between chromosomes 18 and 22 with deletions of 2 and 15 bp, respectively. Although a conserved immunoglobulin recombination signal (7mer-9mer) was absent around the breakpoint on chromosome 18, nonamer-like sequence was recognized within the deleted region at the breakpoint on chromosome 22. No extranucleotide was associated with both joining sites of the t(18;22) translocation. This is in sharp contrast to the t(14;18) translocation involving IgH locus in which the presence of extranucleotides is common and correlates well with the presence and absence of extranucleotides on V-(D)-J joining of IgH and light chain (L) genes, respectively. The data together suggest that the mechanism responsible for the physiological rearrangement of immunoglobulin genes is involved in this translocation.