Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31804490.
- Also identified by DOI 10.1038/s41467-019-13570-y and PMC identifier 6895129.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- B-Lymphocytes
- Cell Transformation, Neoplastic
- Cytidine Deaminase
- Infections
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma