Transcriptomics

Dataset Information

2

A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma [Spleen dataset]


ABSTRACT: Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies. Keywords: Genetic modification, wt vs. transgenic, disease analysis, MALT lymphoma 9 samples were analized of which 5 were splenic lymphomas from Sca1-MALT1 transgenic mice and 4 were spleens from WT mice.

ORGANISM(S): Mus musculus  

SUBMITTER: Jose I Martinez-Ferrandis   Ming Q Du  María B García-Cenador  Cesar Cobaleda  Esther Alonso-Escudero  Jose A Martinez-Climent  Federico Garcia-Bragado  Carolina Vicente-Dueñas  Angela Aznar  Fernando Abollo-Jimenez  Lorena Fontán  Xabier Sagaert  Isidro Sanchez-Garcia  Teresa Flores  Cristina Bertolo  Francisco J Garcia-Criado  Reiner Siebert  Victor Segura  Ellen D Remstein  Izidore S Lossos  Ines Gonzalez-Herrero 

PROVIDER: E-GEOD-25637 | ArrayExpress | 2012-07-09

SECONDARY ACCESSION(S): GSE25637PRJNA142421

REPOSITORIES: GEO, ArrayExpress

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Publications

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.

Vicente-Dueñas Carolina C   Fontán Lorena L   Gonzalez-Herrero Ines I   Romero-Camarero Isabel I   Segura Victor V   Aznar M Angela MA   Alonso-Escudero Esther E   Campos-Sanchez Elena E   Ruiz-Roca Lucía L   Barajas-Diego Marcos M   Sagardoy Ainara A   Martinez-Ferrandis Jose I JI   Abollo-Jimenez Fernando F   Bertolo Cristina C   Peñuelas Ivan I   Garcia-Criado Francisco J FJ   García-Cenador María B MB   Tousseyn Thomas T   Agirre Xabier X   Prosper Felipe F   Garcia-Bragado Federico F   McPhail Ellen D ED   Lossos Izidore S IS   Du Ming-Qing MQ   Flores Teresa T   Hernandez-Rivas Jesus M JM   Gonzalez Marcos M   Salar Antonio A   Bellosillo Beatriz B   Conde Eulogio E   Siebert Reiner R   Sagaert Xavier X   Cobaleda Cesar C   Sanchez-Garcia Isidro I   Martinez-Climent Jose A JA  

Proceedings of the National Academy of Sciences of the United States of America 20120611 26


Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors  ...[more]

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