Immunoglobulin Gene Translocations

Chromosomal translocations involving the immunoglobulin loci are both frequent and critical to the pathogenesis of many chronic lymphoproliferative disorders but are rare in CLL. The incidence of rearrangement involving the BCL2 locus is shown in Table 6-4. Initial studies noted a high incidence of translocation involving the immunoglobulin light-chain loci, but in our own series (unpublished) 10 of 13 cases had t(14:18)(q32q21) translocations. The breakpoints within the BCL2 locus are variable but frequently involve the 5' variable cluster region. Expression of BCL2 protein is high in these cases; however it is not clear whether the level of expression differs from that found in the majority of cases of CLL that express BCL2 protein in the absence of BCL2 gene rearrangements. Many cases of immunoglobulin gene/BCL2 rearrangements are accompanied by trisomy 12, and the BCL2 rearrangement may be the primary or secondary cyto-genetic abnormality.

Translocations involving the immunoglobulin heavy-chain locus on chromosome 14q32 and the BCL3 gene on 19q13 are found in less than 0.5 percent of patients. The breakpoints in the immunoglobulin heavy-chain gene are usually in the switch region upstream of C-alpha 1 or C-alpha 2.42 The BCL3 breakpoints are variable but all result in overexpression of the BCL3 protein, which is an I-KB-like protein. Most cases involve complex cytogenetic abnormalities including trisomy 12.43,44

The t(2;14)(p13;q32) is a rare recurring translocation in B-cell malignancies and has been studied molecularly in four clinically aggressive cases of CLL. A zinc-finger gene (BC211A) is

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