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STAT5-activating oncogenes drive Oncostatin M production causing T cell exhaustion and suppressive myeloid cell recruitment

GSE280685 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/09/26 Platform GPL21103
Summary
Understanding the interplay between oncogenic mutations and immune evasion of cancer cells could help to improve cancer immunotherapy in hematological malignancies. We found that the STAT5-activating oncogenes BCR-ABL, JAK2-V617F, and FLT3-ITD induce Oncostatin M (OSM) which acted immunosuppressive. OSM profoundly reprogrammed bone marrow (BM) stromal cells, inducing the secretion of cytokines connected to T cell exhaustion, including IL-6 and MCP-1. OSM overexpressing mice exhibited reduced T cells numbers, more T cell exhaustion and increased lactic acid production by stroma cells. OSM induced expansion of myeloid-derived suppressor cells (MDSCs) thereby promoting immune escape of malignant hematopoietic cells. Osm knockout reduced disease progression and T cell exhaustion in mice with JAK2-V617F-driven polycythemia vera. Consistently, pharmacological inhibition of OSM reduced disease activity and cytokine production. Our study indicates that STAT5-activating oncogenes drive OSM production thereby inducing MDSC recruitment and T cell exhaustion.
Published in
Oncostatin M induced by STAT5-activating oncogenes promotes disease progression in hematologic malignancies
Rassner M, Müller TA, Crossley KA et al. · Signal transduction and targeted therapy 2025 · PMID 41372120 · doi:10.1038/s41392-025-02491-6
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Also filed as BioProject PRJNA1179960 and SRA study SRP542115. Searching any of these in the dataset finder brings you back here.

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