biostudies-literatureRodriguez-Hernandez GEuropean Research Council5563https://www.ebi.ac.uk/biostudies/studies/S-EPMC6895129biostudies-literatureUnknown10(1)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 pNature communicationsInfectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID.PMC6895129207844Alonso-Lopez DTena-Davila SGRamiro ARRaboso-Gallego JBlanco ORodriguez-Hernandez GOrfao ABorkhardt ACriado FJGSanchez-Garcia IDugas MCenador MBGVicente-Duenas COpitz FVFischer UAlvarez-Prado AFWalter CMuschen MGonzalez-Herrero IRivas JLCasado-Garcia AAuer FDelgado PBartenhagen CHauer JJanssen SfalseInfectious 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 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 p2019-01-01T00:00:00Z2019 Dec2026-05-05T01:01:11.116Z2020-05-21T21:21:09ZS-EPMC68951293180449010.1038/s41467-019-13570-y