| First Author | Rodríguez-Hernández G | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5563 |
| PubMed ID | 31804490 | Mgi Jnum | J:286711 |
| Mgi Id | MGI:6388296 | Doi | 10.1038/s41467-019-13570-y |
| Citation | Rodriguez-Hernandez G, et al. (2019) Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID. Nat Commun 10(1):5563 |
| abstractText | 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. |
