PROGRESSION FROM LYMPHOID HYPERPLASIA TO HIGH-GRADE MALIGNANT-LYMPHOMA IN MICE TRANSGENIC FOR THE T(14, 18)

FOLLICULAR lymphoma, the most common human lymphoma, characteristically has a t(14; 18) interchromosomal translocation 1,2. Its is typically an indolent disease comprised of small resting B cells, but frequently develops into a high-grade lymphoma 3. The t(14; 18) translocates the Bcl-2 gene, generating a deregulated Bcl-2-immunoglobulin fusion gene 4-8. Bcl-2 is a novel inner mitochondrial membrane protein 9 that extends the survival of certain cells by blocking programmed cell death 9-11. To determine the oncogenic potential of the t(14; 18) translocation, we produced transgenic mice bearing a Bcl-2-immunoglobulin minigene that structurally mimicked the t(14; 18) (ref. 12). An indolent follicular hyperplasia in these transgenic mice progressed to a malignant diffuse large-cell lymphoma. The long latency, progression from polyclonal to monoclonal disease, and histological conversion, are all suggestive of secondary changes. Half of the immunoblastic high-grade lymphomas had a rearranged c-myc gene. Our transgenic mice provide an animal model for tumour progression in t(14; 18) lymphoma and show that prolonged B-cell life increases tumour incidence.