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

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 evidenc...

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Detalhes bibliográficos
Autores: Rodríguez-Hernández, Guillermo, Opitz, Friederike V, Delgado, Pilar, Walter, Carolin, Alvarez-Prado, Angel Francisco, 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, Sanchez-Garcia, Isidro, Borkhardt, Arndt
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8953
Acesso em linha:http://hdl.handle.net/20.500.12105/8953
Access Level:acceso abierto
Descrição
Resumo: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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