Detection of additional JH/BCL2 translocations in follicular lymphoma

In vitro enzymatic amplification and direct sequencing were used to detect and characterize t(14;18) recombination junctions in peripheral blood and bone marrow mononuclear cell preparations from patients with follicular lymphoma in remission. Samples from 24/44 patients were found to be positive for translocations involving the major breakpoint region of the BCL2 gene. In samples from seven patients two distinct t(14;18) translocations were shown to be present simultaneously; in one case the second translocation involved the minor cluster region of the BCL2 gene. Biopsy tissue obtained earlier in the course of the disease was available from five of these patients and was shown to contain one of the translocations in each case, but both translocations in only one. Further remission blood and bone marrow samples from the group were also examined. This led to the detection of both translocations in separate samples obtained at different times in a total of four out of the seven cases. In two of the remaining three patients the second translocation could not be amplified from further samples, but in both cases the search led to the identification of a third translocation, again only detectable in a single sample. These findings demonstrate that JH/BCL2 translocations can occur more than once during the course of follicular lymphoma. They suggest that biclonal follicular lymphoma may be more common than has previously been recognized but also raise the possibility that the translocation arises sporadically in the normal lymphoid cells of this group of patients.