{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:35:49Z","timestamp":1786991749847,"version":"build-2736575974"},"reference-count":159,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Interferons (IFNs) are pleiotropic cytokines involved in antiviral defense, immune regulation, and tumor suppression. In myeloproliferative neoplasms (MPNs) and related disorders\u2014including classical BCR, ABL1-negative MPNs, chronic myeloid leukemia (CML), and rarer entities such as chronic neutrophilic leukemia and hypereosinophilic syndromes\u2014disease pathogenesis arises from a spectrum of somatic and structural genetic abnormalities and chronic inflammation, in which IFNs play a paradoxical role. They contribute to disease pathogenesis by promoting abnormal hematopoiesis and immune dysregulation, while also representing a therapeutic option capable of inducing hematologic and molecular remissions. This review outlines the biology and classification of IFNs, focusing on their signaling pathways and downstream effects in both normal and malignant hematopoiesis. We discuss the dual impact of IFN signaling on hematopoietic stem cells, including induction of proliferation, senescence, apoptosis, and DNA damage, and how these mechanisms may both sustain clonal evolution and facilitate disease control. Clinical data supporting the efficacy and safety of IFN-\u03b1, particularly pegylated formulations, in polycythemia vera, essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia are reviewed, along with insights into next-generation IFNs and combination therapies. Understanding the dichotomous effects of IFNs in MPNs not only clarifies their role in disease biology but also informs their optimal use in clinical practice. This duality highlights the need for personalized approaches to IFN-based therapies.<\/jats:p>","DOI":"10.3390\/cancers17213480","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:50:19Z","timestamp":1761785419000},"page":"3480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Dual Role of Interferon Signaling in Myeloproliferative Neoplasms: Pathogenesis and Targeted Therapeutics"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-8337","authenticated-orcid":false,"given":"Valentina","family":"Bonuomo","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, Universit\u00e0 degli Studi di Torino, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Dogliotti","sequence":"additional","affiliation":[{"name":"Division of Hematology 1 U, Department of Biotechnology and Health Sciences, Universit\u00e0 degli Studi di Torino, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Masucci","sequence":"additional","affiliation":[{"name":"Farmacia Clinica Onco-Ematologia, Azienda Ospedaliera Mauriziano di Torino, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selene","family":"Grano","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Savi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Universit\u00e0 degli Studi di Torino, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Frolli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-4791","authenticated-orcid":false,"given":"Daniela","family":"Cilloni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Universit\u00e0 degli Studi di Torino, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-981X","authenticated-orcid":false,"given":"Carmen","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Universit\u00e0 degli Studi di Torino, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","article-title":"Interferons at Age 50: Past, Current and Future Impact on Biomedicine","volume":"6","author":"Borden","year":"2007","journal-title":"Nat. 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