We have determined the frequency with which each of the breakpoint areas of bcl-2 are involved in translocation and are currently investigating whether the specific breakpoints might influence the clinical behavior of lymphoma. We are initiating a study utilizing monoclonal antibodies to the bcl-2 protein (obtained from D. Mason) designed to give us a better understanding of the biological role of this protein in lymphomagenesis and, in particular, lymphoma progression. To adapt PCR technology to the diagnosis of t(14:18) translocated lymphomas, we have developed sets of oligonucleotide primers specific for each of four reported breakpoint clusters so that the majority of t(14:18) translocated lymphomas can be identified. We are studying the feasibility of using PCR to follow response to therapy and predict relapse using peripheral blood samples and in other tissue samples. We are also designing retrospective studies using paraffin embedded tissues. We have shown the bcl-1 breakpoint region is frequently rearranged in malignant lymphoma of intermediate differentiation. We are pursuing this relationship to study the bcl-1 locus and to search for the postulated proto-oncogene which is thought to become activated by the rearrangement event. We have identified and sequenced a delta locus gene rearrangement occurring in over a third or precursor B ALL. We are developing a PCR based blood assay to Detect this common rearrangement as we have done for bcl-2 related lymphomas. To determine whether or not there are biologic differences to justify the continued separation of the undifferentiated lymphoma group into Burkitt-like and non-Burkitt subcategories, we analyzed both groups for abnormalities of oncogene loci commonly associated with lymphoma. We have found molecular genetic differences which support the distinction of these two entities.
