Title: Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice
Authors: Vicente-Duenas, Carolina ×
Fontan, Lorena
Gonzalez-Herrero, Ines
Romero-Camarero, Isabel
Segura, Victor
Angela Aznar, M
Alonso-Escudero, Esther
Campos-Sanchez, Elena
Ruiz-Roca, Lucia
Barajas-Diego, Marcos
Sagardoy, Ainara
Martinez-Ferrandis, Jose I
Abollo-Jimenez, Fernando
Bertolo, Cristina
Penuelas, Ivan
Garcia-Criado, Francisco J
Garcia-Cenador, Maria B
Tousseyn, Thomas
Agirre, Xabier
Prosper, Felipe
Garcia-Bragado, Federico
McPhail, Ellen D
Lossos, Izidore S
Du, Ming-Qing
Flores, Teresa
Hernandez-Rivas, Jesus M
Gonzalez, Marcos
Salar, Antonio
Bellosillo, Beatriz
Conde, Eulogio
Siebert, Reiner
Sagaert, Xavier
Cobaleda, Cesar
Sanchez-Garcia, Isidro
Martinez-Climent, Jose A #
Issue Date: Jun-2012
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:109 issue:26 pages:10534-10539
Abstract: 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 recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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