Oncostatin M induced by STAT5-activating oncogenes promotes disease progression in hematologic malignancies.

ABSTRACT: Understanding the interplay between oncogenic mutations and the tumor microenvironment could help improve therapy for hematological malignancies. We found that the STAT5-activating oncogenes JAK2 p.V617F, FLT3-ITD, and BCR::ABL1 induce oncostatin M (OSM), which triggers disease progression and immunosuppression. The OSM receptor was predominantly expressed on nonhematopoietic bone marrow (BM) stromal cells. OSM reprogrammed these cells via STAT3 and induced the secretion of cytokines connected to T-cell exhaustion, including IL-6 and MCP-1. Compared with control mice, OSM-overexpressing mice presented reduced T-cell numbers, increased levels of inhibitory receptors on T cells, and elevated lactic acid production by BM stromal cells. OSM induced the expansion of myeloid cells which suppress

SUBMITTER: Rassner M 

PROVIDER: S-EPMC12696130 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature