Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/8953
Título
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
Autor(es)
Rodríguez-Hernández, Guillermo | Opitz, Friederike V | Delgado, Pilar CNIC | Walter, Carolin | Alvarez-Prado, Angel Francisco CNIC | González-Herrero, Inés | Auer, Franziska | Fischer, Ute | Janssen, Stefan | Bartenhagen, Christoph | Raboso-Gallego, Javier | Casado-García, Ana | Orfao, Alberto | Blanco, Oscar | Alonso-López, Diego | Rivas, Javier De Las | Tena-Dávila, Sara González de | Müschen, Markus | Dugas, Martin | Criado, Francisco Javier García | Cenador, María Begoña García | Vicente-Dueñas, Carolina | Hauer, Julia | Ramiro, Almudena R CNIC | Sanchez-Garcia, Isidro | Borkhardt, Arndt
Fecha de publicación
2019-12-05
Cita
Nat Commun. 2019; 10(1):5563
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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