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Reduced Myc overexpression and normal B-cell differentiation mediate resistance to avian leukosis virus lymphomagenesis

Oncogene volume 23, pages 4413–4421 (2004)Cite this article

Abstract

Avian leukosis virus (ALV) induces bursal lymphoma in tumor-susceptible chicken strains after proviral integration within the c-myc gene, and subsequent expansion of Myc-overexpressing lymphocytes within transformed follicles. Line 63 strain chickens are resistant to ALV tumorigenesis, largely failing to develop Myc-transformed follicles, although they show similar levels of ALV infection and integration as lymphoma-susceptible strains. Immunohistochemical analysis determined that the transformed follicles that do arise in lymphoma-resistant birds show much lower and more variable Myc overexpression than those of susceptible birds. This reduced Myc overexpression fails to block B-cell differentiation in resistant birds, while high Myc consistently blocks development at a late embryo stage in susceptible birds. This failure of Myc to block differentiation results in a normal pattern of posthatching bursal emigration in resistant transformed follicles, while transformed follicles of susceptible birds grow rapidly due to blocked emigration. Forced Myc overexpression produces transformed follicles in resistant birds, indicating that resistant lymphocytes can tolerate high Myc expression. The coding sequence and expression of the endogenous c-myc gene is the same in resistant and susceptible birds, suggesting that genetic resistance is instead mediated by reduced ALV LTR enhancer-driven transcription in the target lymphocytes of resistant birds.

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Acknowledgements

We thank Donald Ewert and Robert Eisenman for providing monoclonal antibodies, Christine Halbert for a critical reading of the paper, and Gilbert Loring for technical assistance. This work was supported by NCI R01 Grants CA68328 (A Ruddell) and CA20068 (P Neiman).

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, PO Box 19024, MS C2-023, 1100 Fairview Ave. N, Seattle, 98109, WA, USA

    Sean S Parghi, Kimberly A Brandvold, Sandra J Bowers, Paul E Neiman & Alanna Ruddell

  2. Department of Pathology, University of Washington, Seattle, WA, USA

    Paul E Neiman

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  1. Sean S Parghi
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  2. Kimberly A Brandvold
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  4. Paul E Neiman
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  5. Alanna Ruddell
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Correspondence to Alanna Ruddell.

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Parghi, S., Brandvold, K., Bowers, S. et al. Reduced Myc overexpression and normal B-cell differentiation mediate resistance to avian leukosis virus lymphomagenesis. Oncogene 23, 4413–4421 (2004). https://doi.org/10.1038/sj.onc.1207577

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