Nature Communications (Feb 2024)
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,
- Hussein A. Abbas
Affiliations
- Bofei Wang
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Patrick K. Reville
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Mhd Yousuf Yassouf
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Fatima Z. Jelloul
- Department of Hematopathology, Division of Pathology & Laboratory Medicine, The University of Texas MD Anderson Cancer Center
- Christopher Ly
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Poonam N. Desai
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Zhe Wang
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Pamella Borges
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Ivo Veletic
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Enes Dasdemir
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Jared K. Burks
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Guilin Tang
- Department of Hematopathology, Division of Pathology & Laboratory Medicine, The University of Texas MD Anderson Cancer Center
- Shengnan Guo
- School of Basic Medical Sciences, Harbin Medical University
- Araceli Isabella Garza
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Cedric Nasnas
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Nicole R. Vaughn
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Natalia Baran
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Qing Deng
- Department of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Jairo Matthews
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Preethi H. Gunaratne
- Department of Biology and Biochemistry, University of Houston
- Dinler A. Antunes
- Department of Biology and Biochemistry, University of Houston
- Suhendan Ekmekcioglu
- Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Koji Sasaki
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Miriam B. Garcia
- Department of Pediatrics, Division of Pediatrics, The University of Texas MD Anderson Cancer Center
- Branko Cuglievan
- Department of Pediatrics, Division of Pediatrics, The University of Texas MD Anderson Cancer Center
- Dapeng Hao
- School of Basic Medical Sciences, Harbin Medical University
- Naval Daver
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Michael R. Green
- Department of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Marina Konopleva
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Andrew Futreal
- Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Sean M. Post
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Hussein A. Abbas
- Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-024-45916-6
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
