2026-04-27T01:59:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/89532024-10-31T11:57:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Rodríguez-Hernández, Guillermo author Opitz, Friederike V author Delgado, Pilar author Walter, Carolin author Alvarez-Prado, Angel Francisco author González-Herrero, Inés author Auer, Franziska author Fischer, Ute author Janssen, Stefan author Bartenhagen, Christoph author Raboso-Gallego, Javier author Casado-García, Ana author Orfao, Alberto author Blanco, Oscar author Alonso-López, Diego author Rivas, Javier De Las author Tena-Dávila, Sara González de author Müschen, Markus author Dugas, Martin author Criado, Francisco Javier García author Cenador, María Begoña García author Vicente-Dueñas, Carolina author Hauer, Julia author Ramiro, Almudena R author Sanchez-Garcia, Isidro author Borkhardt, Arndt author 2019-12-05 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. Nat Commun. 2019; 10(1):5563 2041-1723 http://hdl.handle.net/20.500.12105/8953 31804490 10.1038/s41467-019-13570-y 2041-1723 Nature communications Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID