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Oncogenic drivers dictate immune control of acute myeloid leukemia.

Nature communications

Authors: Rebecca J Austin, Jasmin Straube, Rohit Halder, Yashaswini Janardhanan, Claudia Bruedigam, Matthew Witkowski, Leanne Cooper, Amy Porter, Matthias Braun, Fernando Souza-Fonseca-Guimaraes, Simone A Minnie, Emily Cooper, Sebastien Jacquelin, Axia Song, Tobias Bald, Kyohei Nakamura, Geoffrey R Hill, Iannis Aifantis, Steven W Lane, Megan J Bywater

Acute myeloid leukemia (AML) is a genetically heterogeneous, aggressive hematological malignancy induced by distinct oncogenic driver mutations. The effect of specific AML oncogenes on immune activation or suppression is unclear. Here, we examine immune responses in genetically distinct models of AML and demonstrate that specific AML oncogenes dictate immunogenicity, the quality of immune response and immune escape through immunoediting. Specifically, expression of Nras alone is sufficient to drive a potent anti-leukemia response through increased MHC Class II expression that can be overcome with increased expression of Myc. These data have important implications for the design and implementation of personalized immunotherapies for patients with AML.

© 2023. The Author(s).

PMID: 37059710

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