Detalle de: Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
| Title | Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID |
| Abstract |
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. Source: Crossref |
| Apa Reference | Rodríguez-Hernández, G., Opitz, F.V., Delgado, P., Walter, C., Álvarez-Prado, Á.F., González-Herrero, I., Auer, F., Fischer, U., Janssen, S., Bartenhagen, C., Raboso-Gallego, J., Casado-García, A., Orfao, A., Blanco, O., Alonso-López, D., Rivas, J.D.L., Tena-Dávila, S.G.d., Müschen, M., Dugas, M., Criado, F.J.G., Cenador, M.B.G., Vicente-Dueñas, C., Hauer, J., Ramiro, A.R., Sanchez-Garcia, I. & Borkhardt, A. (2019). Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID. Nature Communications, 10(1). 10.1038/s41467-019-13570-y |
| Doi | 10.1038/s41467-019-13570-y |
| Publication Date | 5 Dec 2019 |
| Publication Type | Article |
| Ontology | |
| Researchers | Javier De Las Rivas |
| Research Groups | |
| Tools |