Involvement of the BCL3 gene in two patients with chronic lymphocytic leukemia.

The t(14;19)(q32;q13) is a recurring translocation found in some patients with chronic lymphocytic leukemia (CLL), and the t(14;19) juxtaposes the BCL3 gene on chromosome 19 with the immunoglobulin heavy chain gene (IGH) locus on chromosome 14. Genomic DNAs from 49 patients with chronic B-cell leukemia and the related lymphomas were examined by Southern blot hybridization using 2 separate probes, named p alpha 1.4P and p alpha .5B, from the BCL3 gene locus. None of the 18 patients with leukemic manifestations of non-Hodgkin's lymphomas had detectable BCL3 rearrangements. Of 31 patients with CLL, 2 had the BCL3 rearrangements. A comigration study using the C alpha and C epsilon constant gene probe from IGH indicated that the t(14;19) translocation occurred in these 2 patients, and they were diagnosed with CLL/prolymphocytic (PL) according to the French-American-British (FAB) classification. Probes for the IGH locus revealed that leukemia cells of the 2 patients each were clonal, indicating that both small lymphocytes and prolymphocytoid cells found in the peripheral blood of one patient had the t(14;19), as well as a major population of the small lymphocytes in the peripheral blood of a second patient. It thus appears that tumor cells carrying the t(14;19) constitute a distinct disease entity in a group of chronic B-cell leukemia, that has a converting potential to more aggressive forms.