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dc.contributor.author
Morande, Pablo Elías
dc.contributor.author
Yan, Xiao Jie
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Sepulveda Yanez, Julieta Haydee
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Seija, Noé
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Marquez, Maria Elena
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Sotelo, Natalia Soledad
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Abreu, Cecilia
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Crispo, Martina
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Fernández Graña, Gabriel
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Rego, Natalia
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Bois, Therence
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Methot, Stephen Patrick
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Palacios, Florencia
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Remedi, Victoria
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Rai, Kanti R.
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Buschiazzo, Alejandro
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Di Noia, Javier Marcelo
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Navarrete, Marcelo Alejandro
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Chiorazzi, Nicholas
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Oppezzo, Pablo
dc.date.available
2022-05-05T12:04:04Z
dc.date.issued
2021-07
dc.identifier.citation
Morande, Pablo Elías; Yan, Xiao Jie; Sepulveda Yanez, Julieta Haydee; Seija, Noé; Marquez, Maria Elena; et al.; AID overexpression leads to aggressive murine CLL and non-Ig mutations that mirror human neoplasms.; American Society of Hematology; Blood; 7-2021; 1-14
dc.identifier.issn
0006-4971
dc.identifier.uri
http://hdl.handle.net/11336/156606
dc.description.abstract
Most cancers become more dangerous by the outgrowth of malignant subclones with additional DNA mutations that favor proliferation or survival. Using chronic lymphocytic leukemia (CLL), a disease exemplary of this process, and a model for neoplasms in general, we created transgenic mice overexpressing the enzyme, activation-induced deaminase (AID), whose normal function is to induce DNA mutations in B lymphocytes. AID allows normal B lymphocytes to develop more effective immunoglobulin (Ig)-mediated immunity, but also is able to mutate non-Ig genes, predisposing to cancer. In chronic lymphocytic leukemia (CLL), AID expression correlates with poor prognosis suggesting a role for this enzyme in disease progression. Nevertheless, direct experimental evidence identifying the specific genes that are mutated by AID and indicating that those genes are associated with disease progression is not available. To address this point, we overexpressed Aicda in a murine model of CLL (Em-TCL1). Analyses of TCL1/AID mice demonstrate a role for AID in disease kinetics, CLL-cell proliferation, and the development of cancer-related target mutations with canonical AID signatures in non-Igs genes. Notably, our mouse models can accumulate mutations in the same genes that are mutated in human cancers. Moreover, some of these mutations occur at homologous positions, leading to identical or chemically-similar amino acid substitutions as in human CLL and lymphoma.Together, these findings support a direct link between aberrant AID activity and CLL driver mutations that are then selected for their oncogenic effects, whereby AID promotes aggressiveness in CLL and other B-cell neoplasms.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society of Hematology
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CLL
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AID
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EΜ-TCL1 MICE
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MUTATIONS
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
AID overexpression leads to aggressive murine CLL and non-Ig mutations that mirror human neoplasms.
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-03-08T21:18:03Z
dc.journal.pagination
1-14
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Morande, Pablo Elías. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
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Fil: Yan, Xiao Jie. The Feinstein Institute For Medical Research; Estados Unidos
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Fil: Sepulveda Yanez, Julieta Haydee. Universidad de Magallanes; Chile
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Fil: Seija, Noé. Instituto Pasteur de Montevideo; Uruguay
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Fil: Marquez, Maria Elena. Instituto Pasteur de Montevideo; Uruguay
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Fil: Sotelo, Natalia Soledad. Instituto Pasteur de Montevideo; Uruguay
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Fil: Abreu, Cecilia. Instituto Pasteur de Montevideo; Uruguay
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Fil: Crispo, Martina. Instituto Pasteur de Montevideo; Uruguay
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Fil: Fernández Graña, Gabriel. Instituto Pasteur de Montevideo; Uruguay
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Fil: Rego, Natalia. Instituto Pasteur de Montevideo; Uruguay
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Fil: Bois, Therence. Institut de Recherches Cliniques de Montréal; Canadá
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Fil: Methot, Stephen Patrick. Institut de Recherches Cliniques de Montréal; Canadá
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Fil: Palacios, Florencia. The Feinstein Institute For Medical Research; Estados Unidos
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Fil: Remedi, Victoria. Hospital Maciel Montevideo; Uruguay
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Fil: Rai, Kanti R.. The Feinstein Institute For Medical Research; Estados Unidos
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Fil: Buschiazzo, Alejandro. Instituto Pasteur de Montevideo; Uruguay
dc.description.fil
Fil: Di Noia, Javier Marcelo. Institut de Recherches Cliniques de Montréal; Canadá
dc.description.fil
Fil: Navarrete, Marcelo Alejandro. Universidad de Magallanes; Chile
dc.description.fil
Fil: Chiorazzi, Nicholas. The Feinstein Institute For Medical Research; Estados Unidos
dc.description.fil
Fil: Oppezzo, Pablo. Instituto Pasteur de Montevideo; Uruguay
dc.journal.title
Blood
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://ashpublications.org/blood/article/doi/10.1182/blood.2020008654/475401/AID-overexpression-leads-to-aggressive-murine-CLL
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1182/blood.2020008654
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