{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:05:22Z","timestamp":1789268722320,"version":"build-2803163510"},"reference-count":121,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myeloproliferative neoplasms (MPN) are a group of blood cancers in which the bone marrow (BM) produces an overabundance of erythrocyte, white blood cells, or platelets. Philadelphia chromosome-negative MPN has three subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The over proliferation of blood cells is often associated with somatic mutations, such as JAK2, CALR, and MPL. JAK2V617F is present in 95% of PV and 50\u201360% of ET and PMF. Based on current molecular dynamics simulations of full JAK2 and the crystal structure of individual domains, it suggests that JAK2 maintains basal activity through self-inhibition, whereas other domains and linkers directly\/indirectly enhance this self-inhibited state. Nevertheless, the JAK2V617F mutation is not the only determinant of MPN phenotype, as many normal individuals carry the JAK2V617F mutation without a disease phenotype. Here we review the major MPN phenotypes, JAK-STAT pathways, and mechanisms of development based on structural biology, while also describing the impact of other contributing factors such as gene mutation allele burden, JAK-STAT-related signaling pathways, epigenetic modifications, immune responses, and lifestyle on different MPN phenotypes. The cross-linking of these elements constitutes a complex network of interactions and generates differences in individual and cellular contexts that determine the phenotypic development of MPN.<\/jats:p>","DOI":"10.3390\/ijms23031013","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T08:09:20Z","timestamp":1642493360000},"page":"1013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-5663","authenticated-orcid":false,"given":"Panhong","family":"Gou","sequence":"first","affiliation":[{"name":"Laboratoire UMRS-1131, Ecole doctorale 561, Universit\u00e9 de Paris, 75010 Paris, France"},{"name":"INSERM UMR-S1131, H\u00f4pital Saint-Louis, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Zhang","sequence":"additional","affiliation":[{"name":"BFA, UMR 8251, CNRS, Universit\u00e9 de Paris, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Giraudier","sequence":"additional","affiliation":[{"name":"Laboratoire UMRS-1131, Ecole doctorale 561, Universit\u00e9 de Paris, 75010 Paris, France"},{"name":"INSERM UMR-S1131, H\u00f4pital Saint-Louis, 75010 Paris, France"},{"name":"Service de Biologie Cellulaire, H\u00f4pital Saint-Louis, AP-HP, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1182\/blood.V6.4.372.372","article-title":"Some speculations on the myeloproliferative syndromes","volume":"6","author":"Dameshek","year":"1951","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1002\/cncr.24440","article-title":"The 2008 World Health Organization classification system for myeloproliferative neoplasms: Order out of chaos","volume":"115","author":"Tefferi","year":"2009","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1056\/NEJMoa051113","article-title":"A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders","volume":"352","author":"Kralovics","year":"2005","journal-title":"N. 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