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Blocked B cell differentiation and emigration support the early growth of Myc-induced lymphomas

Oncogene volume 20, pages 3226–3234 (2001)Cite this article

Abstract

Avian leukosis virus induces lymphoma in chickens after proviral integration within the c-Myc gene, and subsequent expansion of Myc-overexpressing lymphocytes within transformed bursal follicles. The clonal expansion of these follicles allowed us to examine how Myc influences cell differentiation, growth, and apoptosis in lymphoid progenitors soon after the onset of Myc overexpression. Immunohistochemical analysis of developmental markers established that Myc overexpression consistently blocks lymphocyte differentiation at a late embryonic stage. Myc-transformed follicles also grow much more rapidly than normal follicles. This rapid growth is not mediated by suppression of apoptosis, as normal and Myc-transformed follicles showed similar rates of cell death by TUNEL immunohistochemical analyis of cells undergoing DNA degradation. Measurements of DNA synthesis and mitotic index showed modest effects of Myc to increase lymphocyte proliferation, as normal lymphocytes already divide rapidly. The major mechanism mediating rapid growth of transformed follicles instead involved failure of myc-overexpressing lymphocytes to emigrate from transformed follicles, while normal lymphocytes actively emigrate after hatching, as measured by BrdU pulse-chase labeling and immunohistochemical measurements. This failure to undergo the normal program of differentiation and subsequent bursal retention of lymphocytes accounts for most of the growth of transformed follicles, while Myc-induced proliferation makes a smaller contribution.

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Acknowledgements

We thank Kelly Bird, Sandra Jo Thomas, and Gilbert Loring for technical assistance. This work was supported by NCI RO1 grant CA68328 (A Ruddell), and CA20068 (P Neiman).

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Kimberly A Brandvold, Paul Neiman & Alanna Ruddell

  2. The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania, USA

    Donald L Ewert

  3. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts, USA

    Sally C Kent

  4. Department of Medicine, University of Washington, Seattle, Washington, USA

    Paul Neiman

  5. Department of Pathology, University of Washington, Seattle, Washington, USA

    Paul Neiman

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  1. Kimberly A Brandvold
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Brandvold, K., Ewert, D., Kent, S. et al. Blocked B cell differentiation and emigration support the early growth of Myc-induced lymphomas. Oncogene 20, 3226–3234 (2001). https://doi.org/10.1038/sj.onc.1204431

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