{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:33:02Z","timestamp":1790973182196,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T00:00:00Z","timestamp":1215734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In polycythemia vera (PV) and essential thrombocythemia (ET) specific <jats:italic>JAK2<\/jats:italic> mutations constitutively activate the JAK\u2010STAT pathway, explaining biologic findings such as endogenous erythroid colony (EECs) growth or PRV\u20101 RNA overexpression. Since these markers are detected also in <jats:italic>JAK2<\/jats:italic> wild type patients, we hypothesized that, in these cases, the activation of the JAK\u2010STAT pathway could be produced by a deregulation of the suppressor of cytokine signaling (SOCS) protein system. Eighty\u2010one patients with PV and ET (53 adults and 28 children) were investigated for the methylation status of the <jats:italic>SOCS\u20101<\/jats:italic>, <jats:italic>SOCS\u20102<\/jats:italic> and <jats:italic>SOCS\u20103<\/jats:italic> CpG islands and for several myeloproliferative markers (including <jats:italic>JAK2<\/jats:italic> and <jats:italic>MPL<\/jats:italic> mutations and clonality of hematopoiesis). <jats:italic>SOCS\u20101<\/jats:italic> or <jats:italic>SOCS\u20103<\/jats:italic> hypermethylation was identified in 23 patients and was associated with a significant decrease of SOCS\u20101 or SOCS\u20103 RNA and protein levels. The gene expression was restored by exposing cells to the demethylating agent 2\u2010deoxyazacytidin. Interestingly, <jats:italic>SOCS\u20101<\/jats:italic> or <jats:italic>SOCS\u20103<\/jats:italic> hypermethylation was detected in 6 female patients, proved negative for <jats:italic>JAK2<\/jats:italic> or <jats:italic>MPL<\/jats:italic> mutations and exhibiting monoclonal hematopoiesis. In conclusion, <jats:italic>SOCS\u20101<\/jats:italic> or <jats:italic>SOCS\u20103<\/jats:italic> hypermethylation can activate the JAK\u2010STAT signaling pathway in alternative or together with <jats:italic>JAK2<\/jats:italic> mutations. These alterations might represent a potential therapeutic target. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23694","type":"journal-article","created":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T15:22:49Z","timestamp":1215789769000},"page":"1586-1592","source":"Crossref","is-referenced-by-count":47,"title":["Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative 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