Loss of p73 promotes dissemination of Myc-induced B cell lymphomas in mice

2010 | journal article. A publication with affiliation to the University of Göttingen.

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​Loss of p73 promotes dissemination of Myc-induced B cell lymphomas in mice​
Nemajerova, A.; Petrenko, O.; Truemper, L. H.; Palacios, G. & Moll, U. M.​ (2010) 
Journal of Clinical Investigation120(6) pp. 2070​-2080​.​ DOI: https://doi.org/10.1172/JCI40331 

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Authors
Nemajerova, Alice; Petrenko, Oleksi; Truemper, Lorenz H.; Palacios, Gustavo; Moll, Ute M.
Abstract
Mice engineered to express c-Myc in B cells (E mu-myc mice) develop lethal lymphomas in which the gene encoding the p53 tumor suppressor is frequently mutated. Whether the p53 homolog p73 also functions as a tumor suppressor in vivo remains controversial. Here we have shown that p73 loss does not substantially affect disease onset and mortality in E mu-myc mice. However, it does alter the phenotype of the disease. Specifically, p73 loss decreased nodal disease and increased widespread extranocial dissemination. We further found that p53 acted as the dominant tumor suppressor during the onset of E mu-myc-driven B cell lymphomagenesis, while p73 modulated tumor dissemination and extranodal growth. Immunophenotyping and expression profiling suggested that p73 loss allowed increased maturation of malignant B cells and deregulated genes involved in lymphocyte homing and dissemination of human lymphomas. Consistent with this, p73 expression was frequently downregulated in a large cohort of human mature aggressive B cell lymphomas, and both the incidence and degree of p73 downregulation in these tumors correlated with their extranodal dissemination status. These data indicate that p73 is a modifier of Myc-driven lymphomas in mice, favoring tumor dissemination, and suggest that p73 could be a biomarker for human B cell lymphoma dissemination, a notion that can now be tested in clinicopathologic correlation studies.
Issue Date
2010
Status
published
Publisher
Amer Soc Clinical Investigation Inc
Journal
Journal of Clinical Investigation 
ISSN
0021-9738

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