Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID

[EN]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 evi...

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Detalles Bibliográficos
Autores: Rodríguez Hernández, Guillermo, Opitz, Friederike V., Delgado, Pilar, Walter, Carolin, Álvarez-Prado, Ángel F., González-Herrero, Inés, Auer, Franziska, Fischer, Ute, Janssen, Stefan, Bartenhagen, Christoph, Raboso Gallego, Javier, Casado García, Ana, Orfao de Matos Correia e Vale, José Alberto, Blanco, Oscar, Alonso López, Diego, Rivas Sanz, Javier de las, Tena-Dávila, Sara González de, Müschen, Markus, Dugas, Martin, García Criado, Francisco Javier, García Cenador, María Begoña, Vicente Dueñas, Carolina, Hauer, Julia, Ramiro, Almudena, Sánchez García, Isidro, Borkhardt, Arndt
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/154121
Acceso en línea:http://hdl.handle.net/10366/154121
Access Level:acceso abierto
Palabra clave:Leucemia infantil
Leucemia linfática crónica
3207.13 Oncología
Descripción
Sumario:[EN]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-Bcell 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

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