Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia

The t(14;19)(q32;q13) is a recurring translocation found in leukemic cells of some patients with chronic lymphocytic leukemia (CLL). The BCL3 gene was identified on chromosome 19 adjacent to the breakpoint of the translocation, and has been proposed to be a candidate proto-oncogene which may play a role in leukemogenesis. The current study of a Japanese patient with CLL revealed that the (14;19) is reciprocal at the molecular level; the BCL3 gene was juxtaposed to the 5' side of the S alpha 1 switch region of the immunoglobulin heavy chain gene (IGH) on the der(14) chromosome, and the IGH gene 5' to the S alpha 1 region was joined to chromosome 19 sequences on the der(19) reciprocal partner chromosome. The breakpoint on chromosome 19 was 16 kb upstream of the first exon of the BCL3 gene and 7 bp of chromosome 19 sequences were deleted at the point of the junction. The t(14;19) translocations so far molecularly analyzed consistently occurred within one of the two S alpha switch regions; however, sequence analysis of the chromosome 19 regions involved in the translocation failed to demonstrate an obvious sequence similarity with the switch region. The chromosomal breaks on chromosome 19 from two CLL patients having the t(14;19) were within Alu repeated sequences.