Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies

Bofei Wang, Patrick K. Reville, Mhd Yousuf Yassouf, Fatima Z. Jelloul, Christopher Ly, Poonam N. Desai, Zhe Wang, Pamella Borges, Ivo Veletic, Enes Dasdemir, Jared K. Burks, Guilin Tang, Shengnan Guo, Araceli Isabella Garza, Cedric Nasnas, Nicole R. Vaughn, Natalia Baran, Qing Deng, Jairo Matthews, Preethi H. Gunaratne, Dinler A. Antunes, Suhendan Ekmekcioglu, Koji Sasaki, Miriam B. Garcia, Branko Cuglievan, Dapeng Hao, Naval Daver, Michael R. Green, Marina Konopleva, Andrew Futreal, Sean M. Post and Hussein A. Abbas ()
Additional contact information
Bofei Wang: The University of Texas MD Anderson Cancer Center
Patrick K. Reville: The University of Texas MD Anderson Cancer Center
Mhd Yousuf Yassouf: The University of Texas MD Anderson Cancer Center
Fatima Z. Jelloul: The University of Texas MD Anderson Cancer Center
Christopher Ly: The University of Texas MD Anderson Cancer Center
Poonam N. Desai: The University of Texas MD Anderson Cancer Center
Zhe Wang: The University of Texas MD Anderson Cancer Center
Pamella Borges: The University of Texas MD Anderson Cancer Center
Ivo Veletic: The University of Texas MD Anderson Cancer Center
Enes Dasdemir: The University of Texas MD Anderson Cancer Center
Jared K. Burks: The University of Texas MD Anderson Cancer Center
Guilin Tang: The University of Texas MD Anderson Cancer Center
Shengnan Guo: Harbin Medical University
Araceli Isabella Garza: The University of Texas MD Anderson Cancer Center
Cedric Nasnas: The University of Texas MD Anderson Cancer Center
Nicole R. Vaughn: The University of Texas MD Anderson Cancer Center
Natalia Baran: The University of Texas MD Anderson Cancer Center
Qing Deng: The University of Texas MD Anderson Cancer Center
Jairo Matthews: The University of Texas MD Anderson Cancer Center
Preethi H. Gunaratne: University of Houston
Dinler A. Antunes: University of Houston
Suhendan Ekmekcioglu: The University of Texas MD Anderson Cancer Center
Koji Sasaki: The University of Texas MD Anderson Cancer Center
Miriam B. Garcia: The University of Texas MD Anderson Cancer Center
Branko Cuglievan: The University of Texas MD Anderson Cancer Center
Dapeng Hao: Harbin Medical University
Naval Daver: The University of Texas MD Anderson Cancer Center
Michael R. Green: The University of Texas MD Anderson Cancer Center
Marina Konopleva: The University of Texas MD Anderson Cancer Center
Andrew Futreal: The University of Texas MD Anderson Cancer Center
Sean M. Post: The University of Texas MD Anderson Cancer Center
Hussein A. Abbas: The University of Texas MD Anderson Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient cells. Additionally, IFNγ treatment of primary AML patient cells increased venetoclax resistance. Lastly, a parsimonious 47-gene IFNγ score demonstrates robust prognostic value. In summary, our findings suggest that inhibiting IFNγ is a potential treatment strategy to overcoming venetoclax resistance and immune evasion in AML patients.

Date: 2024
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DOI: 10.1038/s41467-024-45916-6

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