Oncogenic drivers dictate immune control of acute myeloid leukemia

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

doi:10.1038/s41467-023-37592-9

Oncogenic drivers dictate immune control of acute myeloid leukemia

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

Research output: Contribution to journal › Article › Research › peer-review

13 Citations (Scopus)

Abstract

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.

Original language	English
Article number	2155
Number of pages	14
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-37592-9
Publication status	Published - 14 Apr 2023
Externally published	Yes

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Austin, R. J., Straube, J., Halder, R., Janardhanan, Y., Bruedigam, C., Witkowski, M., Cooper, L., Porter, A., Braun, M., Souza-Fonseca-Guimaraes, F., Minnie, S. A., Cooper, E., Jacquelin, S., Song, A., Bald, T., Nakamura, K., Hill, G. R., Aifantis, I., Lane, S. W., & Bywater, M. J. (2023). Oncogenic drivers dictate immune control of acute myeloid leukemia. Nature Communications, 14(1), Article 2155. https://doi.org/10.1038/s41467-023-37592-9

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title = "Oncogenic drivers dictate immune control of acute myeloid leukemia",

abstract = "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 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.",

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

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Austin, RJ, Straube, J, Halder, R, Janardhanan, Y, Bruedigam, C, Witkowski, M, Cooper, L, Porter, A, Braun, M, Souza-Fonseca-Guimaraes, F, Minnie, SA, Cooper, E, Jacquelin, S, Song, A, Bald, T, Nakamura, K, Hill, GR, Aifantis, I, Lane, SW & Bywater, MJ 2023, 'Oncogenic drivers dictate immune control of acute myeloid leukemia', Nature Communications, vol. 14, no. 1, 2155. https://doi.org/10.1038/s41467-023-37592-9

TY - JOUR

T1 - Oncogenic drivers dictate immune control of acute myeloid leukemia

AU - Austin, Rebecca J.

AU - Straube, Jasmin

AU - Halder, Rohit

AU - Janardhanan, Yashaswini

AU - Bruedigam, Claudia

AU - Witkowski, Matthew

AU - Cooper, Leanne

AU - Porter, Amy

AU - Braun, Matthias

AU - Souza-Fonseca-Guimaraes, Fernando

AU - Minnie, Simone A.

AU - Cooper, Emily

AU - Jacquelin, Sebastien

AU - Song, Axia

AU - Bald, Tobias

AU - Nakamura, Kyohei

AU - Hill, Geoffrey R.

AU - Aifantis, Iannis

AU - Lane, Steven W.

AU - Bywater, Megan J.

PY - 2023/4/14

Y1 - 2023/4/14

N2 - 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 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.

AB - 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 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.

UR - https://www.scopus.com/pages/publications/85152564553

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DO - 10.1038/s41467-023-37592-9

M3 - Article

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AN - SCOPUS:85152564553

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2155

ER -

Oncogenic drivers dictate immune control of acute myeloid leukemia

Abstract

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