Rodríguez-Hernández, GuillermoOpitz, Friederike VDelgado, PilarWalter, CarolinAlvarez-Prado, Angel FranciscoGonzález-Herrero, InésAuer, FranziskaFischer, UteJanssen, StefanBartenhagen, ChristophRaboso-Gallego, JavierCasado-García, AnaOrfao, AlbertoBlanco, OscarAlonso-López, DiegoRivas, Javier De LasTena-Dávila, Sara González deMüschen, MarkusDugas, MartinCriado, Francisco Javier GarcíaCenador, María Begoña GarcíaVicente-Dueñas, CarolinaHauer, JuliaRamiro, Almudena RSanchez-Garcia, IsidroBorkhardt, Arndt2020-01-292020-01-292019-12-05Nat Commun. 2019; 10(1):55632041-1723http://hdl.handle.net/20.500.12105/8953The 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.engVoRhttp://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacional31804490101556310.1038/s41467-019-13570-y2041-1723Nature communicationsopen access