Since the functional consequences and clinical relevance of the IFN-γ signaling has not yet been analyzed in MPN, this study analyzed the local IFN-γ expression and IFN-γ signaling in cell supernatants and the BM TME in (i) two human JAK2 V617F-mutated cell lines in vitro, (ii) in BMB of 265 MPN patients with known driver mutations and clinical parameters including patients’ outcome as well as 50 non-neoplastic BM (nnBM) cases, (iii) its correlation to the immune cell composition of the bone marrow (BM) TME and (iv) expression of immune response relevant factors, like ICP molecules and HLA-I. This evidence concerns the gene IFNG and myeloproliferative neoplasm.