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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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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Perforin
B-Cell Lymphoma
B-Lymphocytes
Immunoglobulin Heavy Chains
Oncogenes
Lymphoma
Neoplasms
Alleles

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., ... 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

Perforin-mediated suppression of B-cell lymphoma. / Bolitho, Paul; Street, Shayna E A; Westwood, Jennifer A.; Edelmann, Winfried; MacGregor, Duncan; Waring, Paul; Murray, William K.; Godfrey, Dale I.; Trapani, Joseph A.; Johnstone, Ricky W.; Smyth, Mark J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 8, 24.02.2009, p. 2723-2728.

Research output: Contribution to journalArticle

Bolitho, P, Street, SEA, Westwood, JA, Edelmann, W, MacGregor, D, Waring, P, Murray, WK, Godfrey, DI, Trapani, JA, Johnstone, RW & Smyth, MJ 2009, 'Perforin-mediated suppression of B-cell lymphoma', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2723-2728. https://doi.org/10.1073/pnas.0809008106
Bolitho, Paul ; Street, Shayna E A ; Westwood, Jennifer A. ; Edelmann, Winfried ; MacGregor, Duncan ; Waring, Paul ; Murray, William K. ; Godfrey, Dale I. ; Trapani, Joseph A. ; Johnstone, Ricky W. ; Smyth, Mark J. / Perforin-mediated suppression of B-cell lymphoma. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 8. pp. 2723-2728.
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