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. It is typically an indolent disease comprised of small resting B cells, but frequently develops into a high-grade lymphoma. The t(14; 18) translocates the Bcl-2 gene, generating a deregulated Bcl-2-immunoglobulin fusion gene. Bcl-2 is a novel inner mitochondrial membrane protein that extends the survival of certain cells by blocking programmed cell death. 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). 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.
McDonnell
T J
TJ
Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110.
Korsmeyer
S J
SJ
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D008221:Lymphoid Tissue / Q000473:pathology*; D008223:Lymphoma / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D014178:Translocation, Genetic