Oncogenic drivers dictate immune control of acute myeloid leukemia

Author:

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

Abstract

AbstractAcute 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 NrasG12D 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.

Funder

Department of Health | National Health and Medical Research Council

Leukaemia Foundation

CSL Centenary Fellowship (SWL), Herron Family Trust, Gordon and Jessie Gilmour

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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