{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:44:32Z","timestamp":1775612672606,"version":"3.50.1"},"reference-count":181,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"J.L.V and A.G.-H. research are supported by PIUNA 2020 program of the University of Navarra.","award":["Code 15058203"],"award-info":[{"award-number":["Code 15058203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ph-negative myeloproliferative neoplasms (polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)) are infrequent blood cancers characterized by signaling aberrations. Shortly after the discovery of the somatic mutations in JAK2, MPL, and CALR that cause these diseases, researchers extensively studied the aberrant functions of their mutant products. In all three cases, the main pathogenic mechanism appears to be the constitutive activation of JAK2\/STAT signaling and JAK2-related pathways (MAPK\/ERK, PI3K\/AKT). However, some other non-canonical aberrant mechanisms derived from mutant JAK2 and CALR have also been described. Moreover, additional somatic mutations have been identified in other genes that affect epigenetic regulation, tumor suppression, transcription regulation, splicing and other signaling pathways, leading to the modification of some disease features and adding a layer of complexity to their molecular pathogenesis. All of these factors have highlighted the wide variety of cellular processes and pathways involved in the pathogenesis of MPNs. This review presents an overview of the complex signaling behind these diseases which could explain, at least in part, their phenotypic heterogeneity.<\/jats:p>","DOI":"10.3390\/cancers13050984","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A Broad Overview of Signaling in Ph-Negative Classic Myeloproliferative Neoplasms"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-7744","authenticated-orcid":false,"given":"Ana","family":"Guijarro-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7416-3679","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Vizmanos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/sj.leu.2404955","article-title":"Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms","volume":"22","author":"Tefferi","year":"2008","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJM200104053441402","article-title":"Activity of a specific inhibitor of the bcr-abl tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome","volume":"344","author":"Druker","year":"2001","journal-title":"N. 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