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Human\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F-mutated cell lines, 265 bone marrow biopsies (BMB) of two MPN cohorts, and 50 non-neoplastic BMB, revealed an intrinsic activation of IFN-\u03b3 signaling, which was confirmed by public RNA expression data. In vitro analysis of\n                    <jats:italic>JAK2<\/jats:italic>\n                    -mutated cell lines showed an activation of IFN-\u03b3 signaling pathway in the absence of IFN-\u03b3 in the cell supernatants. In addition, a heterogeneous, but increased expression of IFN-\u03b3 signaling components was found in BMB of\n                    <jats:italic>JAK2<\/jats:italic>\n                    -mutated samples with the highest expression in lymphocytes and monocytes, accompanied by increased tumor infiltrating lymphocytes (TIL). Unsupervised clustering identified a prognostic favorable cluster in both patient cohorts characterized by augmented IFN-\u03b3 signaling and TILs. This cluster was enriched with\n                    <jats:italic>JAK2<\/jats:italic>\n                    -mutated, JAK-inhibition naive MPN, mainly essential thrombocythemia and polycythemia vera with mild bone marrow fibrosis. Moreover, in silico data confirmed the link between\n                    <jats:italic>JAK2<\/jats:italic>\n                    mutations and increased IFN-\u03b3 signaling. Multivariate Cox regression revealed TILs to be the strongest prognostic marker. In conclusion,\n                    <jats:italic>JAK2<\/jats:italic>\n                    -mutated MPN exhibit an intrinsic activation of IFN-\u03b3 signaling associated with changes in the BM TME and patients\u2019 outcome.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02706-3","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:43:18Z","timestamp":1754401398000},"page":"2391-2405","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-\u03b3 signaling and driver mutations"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-6831","authenticated-orcid":false,"given":"Marcus","family":"Bauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoforos","family":"Vaxevanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-515X","authenticated-orcid":false,"given":"Nadja","family":"Jaekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-3841","authenticated-orcid":false,"given":"Hubert","family":"Hackl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wilfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Zoellig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Haemmerle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-5232","authenticated-orcid":false,"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-2239","authenticated-orcid":false,"given":"Haifa Kathrin","family":"Al-Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Seliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wickenhauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"2706_CR1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1182\/blood.2019000943","volume":"136","author":"AJ Dunbar","year":"2020","unstructured":"Dunbar AJ, Rampal RK, Levine R. 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