{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:36:13Z","timestamp":1790004973415,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T00:00:00Z","timestamp":1361491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,5]]},"abstract":"Summary<\/jats:title>The significance of loss of SOCS<\/jats:styled-content>3, a negative regulator of signalling pathways including those of STAT<\/jats:styled-content>3 and NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B<\/jats:styled-content>,<\/jats:italic> was examined in mantle cell lymphoma (MCL<\/jats:styled-content>). The protein expression and gene methylation status of SOCS<\/jats:styled-content>3<\/jats:italic> were detected using immunohistochemistry\/W<\/jats:styled-content>estern blots and methylation\u2010specific polymerase chain reaction, respectively. To evaluate its functional importance, SOCS<\/jats:styled-content>3 was restored in two SOCS<\/jats:styled-content>3\u2010negative MCL<\/jats:styled-content> cell lines using a lentiviral vector. Loss of SOCS<\/jats:styled-content>3 protein expression was found in 3\/4 MCL<\/jats:styled-content> cell lines and 18\/33 (54\u00b75%) tumours. SOCS3<\/jats:italic> was found consistently methylated in cell lines (3\/4) and tumours (7\/7) negative for SOCS<\/jats:styled-content>3, and was unmethylated in all SOCS<\/jats:styled-content>3\u2010positive cell line (1\/1) and tumours (5\/5) examined. Treatment of all three SOCS<\/jats:styled-content>3\u2010negative cell lines with 2\u2032\u2010deoxy\u20105\u2010azacytidine restored SOCS<\/jats:styled-content>3 expression. SOCS<\/jats:styled-content>3 is biologically important in MCL<\/jats:styled-content>, as lentiviral transfer of SOCS<\/jats:styled-content>3<\/jats:italic> in SOCS<\/jats:styled-content>3\u2010negative cell lines increased their apoptotic activity, downregulated nuclear factor (NF<\/jats:styled-content>)\u2010\u03ba<\/jats:italic>B\u2010p65, cyclin D<\/jats:styled-content>1 (CCND1<\/jats:styled-content>), BCL<\/jats:styled-content>2 and BCL\u2010XL<\/jats:styled-content> (BCL2L1), and substantially dampened interleukin 10\u2010induced STAT<\/jats:styled-content>3 activation. In 19 patients aged \u226469\u00a0years at time of diagnosis, we found that those that carried SOCS<\/jats:styled-content>3\u2010negative tumours showed a trend toward a worse outcome (P<\/jats:italic>\u00a0=\u00a00\u00b71, log\u2010rank).<\/jats:p>","DOI":"10.1111\/bjh.12262","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T05:53:38Z","timestamp":1361512418000},"page":"348-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Gene methylation and silencing of SOCS<\/scp>3<\/i> in mantle cell lymphoma"],"prefix":"10.1111","volume":"161","author":[{"given":"Ommoleila","family":"Molavi","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology 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