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 CHROMOSOME-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.