Proceedings of the National Academy of Sciences of the United States of America, 2012. 109(26): p. 10534-9. Epub 2012 Jun 11. PMID:22689981


Vicente-Duenas, C., L. Fontan, I. Gonzalez-Herrero, I. Romero-Camarero, V. Segura, M.A. Aznar, E. Alonso-Escudero, E. Campos-Sanchez, L. Ruiz-Roca, M. Barajas-Diego, A. Sagardoy, J.I. Martinez-Ferrandis, F. Abollo-Jimenez, C. Bertolo, I. Penuelas, F.J. Garcia-Criado, M.B. Garcia-Cenador, T. Tousseyn, X. Agirre, F. Prosper, F. Garcia-Bragado, E.D. McPhail, I.S. Lossos, M.Q. Du, T. Flores, J.M. Hernandez-Rivas, M. Gonzalez, A. Salar, B. Bellosillo, E. Conde, R. Siebert, X. Sagaert, C. Cobaleda, I. Sanchez-Garcia, and J.A. Martinez-Climent.


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.


En el trabajo publicado en la revista PNAS se describe cómo han conseguido reproducir la patología humana en el ratón con una aproximación experimental muy novedosa. La patología estudiada es un tipo de enfermedad denominado Linfoma MALT (linfoma localizado en el tejido linfoide asociado a mucosas) y se ha utilizado una aproximación experimental que permite y limita la expresión de un oncogén (MALT1) a células stem o progenitores dentro del sistema hematopoyético. De este modo, se demuestra por primera vez que es posible reproducir las características histológicas y moleculares de la enfermedad humana en ratón. En consecuencia, se ha generado un nuevo modelo de ratón donde probar posibles terapias frente a esta enfermedad. Por último, estos resultados sugieren que las células stem o progenitores celulares del sistema hematopoyético pueden estar implicadas en la patogénesis de los linfomas en humanos, un hecho hasta ahora no descrito.

imagen noviembre


Este trabajo es el fruto de la colaboración de diferentes grupos de investigación. Los ratones han sido generados y caracterizados por grupos del CSIC pertenecientes al Instituto de Biología Molecular y Celular del Cáncer de Salamanca (CSIC-Universidad de Salamanca) y al Centro de Biologia Molecular Severo Ochoa de Madrid (CBMSO). El modelo de ratón generado ha sido comparado con la patología humana mediante análisis de expresión génica en el Centro de Investigación Médica Aplicada de Pamplona (CIMA).

Para ver el artículo completo, pulse aqui

Más artículos en la revista SEBBM.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction


Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oli- gomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin...

Read more

Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour


To satisfy its high energetic demand, the brain depends on the metabolic cooperation of various cell types. For example, astrocytic-derived lactate sustains memory consolidation by serving both as an oxidizable...

Read more

Glucose restriction promotes osteocyte specification by activating a PGC-1α-dependent transcriptional program


Osteocytes, the most abundant of bone cells, differentiate while they remain buried within the bone matrix. This encasement limits their access to nutrients and likely affects their differentiation, a process...

Read more

ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements


/Bacillus subtilis/ ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA...

Read more

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer


Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Read more

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton


Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Read more

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice


Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Read more

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons


Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Read more

Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions


Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts...

Read more

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures


DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Read more

Protector Members