3 results on '"González de Tena‐Dávila, Sara"'
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2. Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
- Author
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Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, German Cancer Aid, Josep Carreras Leukemia Foundation, European Research Council, Asociación Española Contra el Cáncer, Centro Nacional de Investigaciones Oncológicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), German Childhood Cancer Foundation, Federal Ministry of Education and Research (Germany), Junta de Castilla y León, Rodríguez-Hernández, Guillermo, Opitz, Friederike V., Delgado, Pilar, Walter, Carolin, Álvarez-Prado, Angel Francisco, González-Herrero, Inés, Auer, Franziska, Fischer, Ute, Janssen, Stefan, Bartenhagen, Christoph, Raboso-Gallego, Javier, Casado-García, Ana, Orfao, Alberto, Blanco, Óscar, Alonso-López, D., Rivas, Javier de las, González de Tena-Dávila, Sara, Müschen, Markus, Dugas, Martin, García-Criado, Francisco Javier, García-Cenador, Begoña, Vicente-Dueñas, Carolina, Hauer, Julia, Ramiro, Almudena R., Sánchez García, Isidro, Borkhardt, Arndt, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, German Cancer Aid, Josep Carreras Leukemia Foundation, European Research Council, Asociación Española Contra el Cáncer, Centro Nacional de Investigaciones Oncológicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), German Childhood Cancer Foundation, Federal Ministry of Education and Research (Germany), Junta de Castilla y León, Rodríguez-Hernández, Guillermo, Opitz, Friederike V., Delgado, Pilar, Walter, Carolin, Álvarez-Prado, Angel Francisco, González-Herrero, Inés, Auer, Franziska, Fischer, Ute, Janssen, Stefan, Bartenhagen, Christoph, Raboso-Gallego, Javier, Casado-García, Ana, Orfao, Alberto, Blanco, Óscar, Alonso-López, D., Rivas, Javier de las, González de Tena-Dávila, Sara, Müschen, Markus, Dugas, Martin, García-Criado, Francisco Javier, García-Cenador, Begoña, Vicente-Dueñas, Carolina, Hauer, Julia, Ramiro, Almudena R., Sánchez García, Isidro, and Borkhardt, Arndt
- Abstract
The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development.
- Published
- 2019
3. Lmo2 expression defines tumor cell identity during T-cell leukemogenesis
- Author
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Josep Carreras Leukemia Foundation, University of Applied Sciences Bonn-Rhein-Sieg, German Childhood Cancer Foundation, Federal Ministry of Education and Research (Germany), European Commission, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Inocente Inocente, García-Ramírez, Idoia, Bhatia, Sanil, Rodríguez-Hernández, Guillermo, González-Herrero, Inés, Walter, Carolin, González de Tena-Dávila, Sara, Parvin, Salma, Haas, Oskar, Woessmann, Wilhelm, Stanulla, Martin, Schrappe, Martin, Dugas, Martin, Natkunam, Yasodha, Orfao, Alberto, Domínguez, Verónica, Pintado, Belén, Blanco, Óscar, Alonso-López, D., Rivas, Javier de las, Martín-Lorenzo, Alberto, Jiménez, Rafael, García-Criado, Francisco Javier, García-Cenador, Begoña, Lossos, Izidore S., Vicente-Dueñas, Carolina, Borkhardt, Arndt, Hauer, Julia, Sánchez García, Isidro, Josep Carreras Leukemia Foundation, University of Applied Sciences Bonn-Rhein-Sieg, German Childhood Cancer Foundation, Federal Ministry of Education and Research (Germany), European Commission, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Inocente Inocente, García-Ramírez, Idoia, Bhatia, Sanil, Rodríguez-Hernández, Guillermo, González-Herrero, Inés, Walter, Carolin, González de Tena-Dávila, Sara, Parvin, Salma, Haas, Oskar, Woessmann, Wilhelm, Stanulla, Martin, Schrappe, Martin, Dugas, Martin, Natkunam, Yasodha, Orfao, Alberto, Domínguez, Verónica, Pintado, Belén, Blanco, Óscar, Alonso-López, D., Rivas, Javier de las, Martín-Lorenzo, Alberto, Jiménez, Rafael, García-Criado, Francisco Javier, García-Cenador, Begoña, Lossos, Izidore S., Vicente-Dueñas, Carolina, Borkhardt, Arndt, Hauer, Julia, and Sánchez García, Isidro
- Abstract
The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL. In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL. The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL. We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.
- Published
- 2018
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