Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18) (original) (raw)

Nature volume 349, pages 254–256 (1991)Cite this article

Abstract

FOLLICULAR lymphoma, the most common human lymphoma, characteristically has a t(14;18) interchromosomal translocation1,2. It is typically an indolent disease comprised of small resting B cells, but frequently develops into a high-grade lymphoma3. The t(14; 18) translocates the Bcl-2 gene, generating a deregulated _Bcl-2_–immunoglobulin fusion gene4–8. Bcl-2 is a novel inner mitochondrial membrane protein9 that extends the survival of certain cells by blocking programmed cell death9–11. 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.

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Authors and Affiliations

  1. The Howard Hughes Medical Institute and the Departments of Medicine, Molecular Microbiology and Pathology, Washington University School of Medicine, 660 South Euclid, St Louis, Missouri, 63110, USA
    Timothy J. McDonnell & Stanley J. Korsmeyer

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  1. Timothy J. McDonnell
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  2. Stanley J. Korsmeyer
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McDonnell, T., Korsmeyer, S. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18).Nature 349, 254–256 (1991). https://doi.org/10.1038/349254a0

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