{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:56:24Z","timestamp":1755798984754,"version":"3.37.3"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed methylation\u2010specific <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>) analysis of the <jats:italic><jats:styled-content style=\"fixed-case\">PRDM<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>3,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>73<\/jats:italic> genes in 61 patients with <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> (43 chronic phase, <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>; two accelerated phase; and 16 blast crisis, <jats:styled-content style=\"fixed-case\">BC<\/jats:styled-content>). Oxidative <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> PCR<\/jats:styled-content>\u2010single\u2010strand conformation polymorphism, and real\u2010time reverse transcriptase <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> were also analyzed. K\u2010562 cells were grown in the presence of 5\u2010Aza\u2010<jats:styled-content style=\"fixed-case\">dC<\/jats:styled-content> and trichostatin A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Methylation of the <jats:italic><jats:styled-content style=\"fixed-case\">PRDM<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>3,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>73<\/jats:italic> genes was detected in 24\/60 (40%), 21\/61 (34%), and 28\/60 (47%) patients, respectively. Methylation of all three genes was detected in 19\/59 (32%) patients. Methylation was more frequent in <jats:styled-content style=\"fixed-case\">BC<\/jats:styled-content> than in <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>. Oxidative <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analysis detected 5\u2010<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content> in the <jats:italic><jats:styled-content style=\"fixed-case\">PRDM<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>3,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>73<\/jats:italic> genes in 10\/22 (45%), 15\/21 (71%), and 16\/26 (62%) samples with methylation detected by <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K\u2010562 cells induced growth suppression, demethylation, and reexpression of the <jats:italic><jats:styled-content style=\"fixed-case\">PRDM<\/jats:styled-content>2<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">RUNX<\/jats:styled-content>3<\/jats:italic> genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Multiple tumor suppressor genes on 1p were inactivated in <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> by methylation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12857","type":"journal-article","created":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T21:38:05Z","timestamp":1485553085000},"page":"467-477","source":"Crossref","is-referenced-by-count":3,"title":["Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous 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