{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:38:55Z","timestamp":1764175135565,"version":"3.37.3"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interferon regulatory factor 4 (<jats:italic>IRF4<\/jats:italic>) is involved in the pathogenesis of various hematologic malignancies. Its expression has been related to the negative regulation of myeloid-derived suppressor cells (MDSCs) and the polarization of anti-inflammatory M2 macrophages, thereby altering immunosurveillance and inflammatory mechanisms. An abnormal inflammatory status in the bone marrow microenvironment of myeloproliferative neoplasms (MPNs) has recently been demonstrated; moreover, in chronic myeloid leukemia a downregulated expression of <jats:italic>IRF4<\/jats:italic> has been found. In this context, we evaluated the <jats:italic>IRF4<\/jats:italic> expression in 119 newly diagnosed consecutive Philadelphia negative MPNs (Ph- MPNs), showing a low expression among the MPNs phenotypes with a more significant decrease in primary myelofibrosis patients. Lower <jats:italic>IRF4<\/jats:italic> levels were associated with <jats:italic>JAK2<\/jats:italic>\u2009+\u2009and triple negatives cases carrying the worst prognosis. Furthermore, the <jats:italic>IRF4<\/jats:italic> levels were related to leukemic transformation and a shorter leukemia-free survival; moreover, the risk of myelofibrosis transformation in polycythemia vera and essential thrombocythemia patients was more frequent in cases with lower <jats:italic>IRF4<\/jats:italic> levels. Overall, our study demonstrates an <jats:italic>IRF4<\/jats:italic> dysregulated expression in MPNs patients and its association with a worse prognosis. Further studies could validate these data, to improve our knowledge of the MPNs pathogenesis and confirm the <jats:italic>IRF4<\/jats:italic> role as a new prognostic factor.<\/jats:p>","DOI":"10.1186\/s40164-021-00253-y","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T05:02:28Z","timestamp":1640322148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IRF4 expression is low in Philadelphia negative myeloproliferative neoplasms and is associated with a worse prognosis"],"prefix":"10.1186","volume":"10","author":[{"given":"Cosimo","family":"Cumbo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Tarantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Anelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Zagaria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immacolata","family":"Redavid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crescenzio Francesco","family":"Minervini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Coccaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Tota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Ricco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Parciante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosa","family":"Conserva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgina","family":"Specchia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pellegrino","family":"Musto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7926-6052","authenticated-orcid":false,"given":"Francesco","family":"Albano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"253_CR1","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.4161\/onci.22475","volume":"1","author":"H Yanai","year":"2012","unstructured":"Yanai H, Negishi H, Taniguchi T. The IRF family of transcription factors inception, impact and implications in oncogenesis. Oncoimmunology. 2012;1:1376\u201386.","journal-title":"Oncoimmunology"},{"key":"253_CR2","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.3390\/jcm9082334","volume":"9","author":"L Longhitano","year":"2020","unstructured":"Longhitano L, Li Volti G, Giallongo C, Spampinato M, Barbagallo I, Di Rosa M, et al. The role of inflammation and inflammasome in myeloproliferative disease. J Clin Med. 2020;9:2334.","journal-title":"J Clin Med"},{"key":"253_CR3","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/ni.1920","volume":"11","author":"T Satoh","year":"2010","unstructured":"Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. 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Front Med. 2021. https:\/\/doi.org\/10.1007\/s11684-021-0858-1.","journal-title":"Front Med"},{"key":"253_CR6","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1182\/blood-2008-07-170449","volume":"113","author":"F Cervantes","year":"2009","unstructured":"Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International working group for myelofibrosis research and treatment. Blood. 2009;113:2895\u2013901. https:\/\/doi.org\/10.1182\/blood-2008-07-170449.","journal-title":"Blood"},{"key":"253_CR7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.humpath.2018.02.023","volume":"80","author":"N Coccaro","year":"2018","unstructured":"Coccaro N, Zagaria A, Orsini P, Anelli L, Tota G, Casieri P, et al. RARA and RARG gene downregulation associated with EZH2 mutation in acute promyelocytic-like morphology leukemia. 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Informed consent was obtained from all patients before study inclusion, in accordance with the Declaration of Helsinki. Patients' records\/information were anonymized and de-identified before analysis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent for publication was obtained from patients before their enrolment in the present study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}