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Título
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
Autor(es)
Palabras clave
Leucemia infantil
Leucemia linfática crónica
Clasificación UNESCO
3207.13 Oncología
Fecha de publicación
2019
Editor
Nature Research
Resumen
[EN]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-Bcell
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
URI
DOI
10.1038/s41467-019-13570-y
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