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Effect of A20 deletion in a retroviral mouse model of AML

GSE250372 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/09/03 Platform GPL17021
Summary
We show that AML patients who experience induction failure have elevated expression of the NF-kB target gene TNFAIP3/A20 and impaired necroptotic cell death, leading to a worse prognosis with chemotherapy. A20High AML samples display resistance to anthracyclines, while A20Low AML samples show sensitivity. Loss of A20 in AML cells restores sensitivity to anthracycline treatment by inducing necroptosis. Moreover, our studies revealed that A20 plays a critical role in AML development as deletion or knockdown of A20 effectively suppresses leukemic cells by mediating spontaneous necroptosis. A20 prevents necroptosis in AML by targeting the necroptosis effector RIPK1, and anthracycline-induced necroptosis is abrogated in A20High AML cells. These findings suggest that NF-kB-driven A20 overexpression plays a role in failed chemotherapy induction and highlights the potential of targeting an alternative cell death pathway in AML. The data contained here provide a platform in which to examine the effects of A20 loss in a retroviral mouse model of AML.
Published in
Chemotherapy resistance in acute myeloid leukemia is mediated by A20 suppression of spontaneous necroptosis
Culver-Cochran AE, Hassan A, Hueneman K et al. · Nature communications 2024 · PMID 39448591 · doi:10.1038/s41467-024-53629-z
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Also filed as BioProject PRJNA1053615 and SRA study SRP478374. Searching any of these in the dataset finder brings you back here.

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