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

AuthorsRodríguez-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
Issue Date2019
PublisherSpringer Nature
CitationNature Communications 10: 5563 (2019)
AbstractThe 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.
Publisher version (URL)https://doi.org/10.1038/s41467-019-13570-y
Appears in Collections:(IBMCC) Artículos
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