Association of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-γ signaling and driver mutations.

ABSTRACT: Constitutive JAK/STAT pathway activation is crucial in the pathogenesis of BCR::ABL1-negative myeloproliferative neoplasms (MPN), but has not yet been linked to interferon (IFN)-γ signaling and tumor microenvironment. Human JAK2 V617F-mutated cell lines, 265 bone marrow biopsies (BMB) of two MPN cohorts, and 50 non-neoplastic BMB, revealed an intrinsic activation of IFN-γ signaling, which was confirmed by public RNA expression data. In vitro analysis of JAK2-mutated cell lines showed an activation of IFN-γ signaling pathway in the absence of IFN-γ in the cell supernatants. In addition, a heterogeneous, but increased expression of IFN-γ signaling components was found in BMB of JAK2-mutated samples with the highest expression in lymphocytes and monocytes, accompanied by increased tumor infil

SUBMITTER: Bauer M 

PROVIDER: S-EPMC12463677 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature