Perforin-mediated suppression of B-cell lymphoma

Paul Bolitho, Shayna E.A. Street, Jennifer A. Westwood, Winfried Edelmann, Duncan MacGregor, Paul Waring, William K. Murray, Dale I. Godfrey, Joseph A. Trapani, Ricky W. Johnstone, Mark J. Smyth

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31 Scopus citations

Abstract

In the present study, we have examined the effect of perforin (pfp) deficiency in 4 models of mouse B-cell lymphomagenesis. We have examined pfp loss on the background of either Mlh1 tumor suppressor allele loss or oncogene expression [Ig heavy chain (Eμ)-v-Abl, Eμ-myc, and vav-bcl2]. Pfp was shown to act as a suppressor of B-cell malignancies characteristically driven by v-Abl or bcl-2, whereas Mlh loss cooperated in accelerating spontaneous B-cell lymphomas characteristic of pfp loss. No protective role for pfp was observed in the more aggressive Eμ-myc model of B-cell lymphoma. These transgenic models have allowed us to distinguish the role of pfp in surveillance of B-cell lymphomagenesis, as opposed to its loss simply driving the onset of a spontaneous lymphoma characteristic of pfp deficiency.

Original languageEnglish (US)
Pages (from-to)2723-2728
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number8
DOIs
StatePublished - Feb 24 2009

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Keywords

  • Lymphomagenesis
  • Transgenic mice
  • Tumor surveillance

ASJC Scopus subject areas

  • General

Cite this

Bolitho, P., Street, S. E. A., Westwood, J. A., Edelmann, W., MacGregor, D., Waring, P., Murray, W. K., Godfrey, D. I., Trapani, J. A., Johnstone, R. W., & Smyth, M. J. (2009). Perforin-mediated suppression of B-cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2723-2728. https://doi.org/10.1073/pnas.0809008106