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Oncogenic drivers dictate immune control of acute myeloid leukemia

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 AM...

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Detalles Bibliográficos
Autores principales: Austin, Rebecca J., Straube, Jasmin, Halder, Rohit, Janardhanan, Yashaswini, Bruedigam, Claudia, Witkowski, Matthew, Cooper, Leanne, Porter, Amy, Braun, Matthias, Souza-Fonseca-Guimaraes, Fernando, Minnie, Simone A., Cooper, Emily, Jacquelin, Sebastien, Song, Axia, Bald, Tobias, Nakamura, Kyohei, Hill, Geoffrey R., Aifantis, Iannis, Lane, Steven W., Bywater, Megan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104832/
https://www.ncbi.nlm.nih.gov/pubmed/37059710
http://dx.doi.org/10.1038/s41467-023-37592-9
Descripción
Sumario: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(G12D) 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.