{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T14:37:15Z","timestamp":1725892635132},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T00:00:00Z","timestamp":1350345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Human Disabled\u20102 (<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2), a putative tumor suppressor gene, is frequently down\u2010regulated in human tumors. This study aims to explore the association between <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 methylation status and expression in newly diagnosed myelodysplastic syndrome (<jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>) patients and patients who received 5\u2010aza\u20102\u2032\u2010deoxycytidine (decitabine) treatment, so as to determine the effect of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 in the pathogenesis of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Methylation\u2010specific polymerase chain reaction and bisulfite sequencing were used to detect the methylation status of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 gene. <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 expression was investigated by using fluorescence quantitation <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">FQRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>) and western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypermethylation of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 gene was present in 50.6% of patients with <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> and was significantly correlated with the down\u2010regulation of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression. There was a significant difference in methylation frequency between refractory anemia\/refractory anemia with ringed sideroblasts\/<jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> associated with isolated del (5q) (<jats:styled-content style=\"fixed-case\">RA\/RARS<\/jats:styled-content>\/5q\u2010) group (33.3%) and refractory anemia with excess blasts\u20101\/\u20102 (<jats:styled-content style=\"fixed-case\">RAEB<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">RAEB<\/jats:styled-content>\u20102) group (73.3%). Significant difference was also observed between refractory cytopenia with multiline dysplasia group (37.8%) and <jats:styled-content style=\"fixed-case\">RAEB<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">RAEB<\/jats:styled-content>\u20102 group. In addition, higher frequency of hypermethylation was observed in intermediate\u20102\u2010\/high\u2010risk group, compared to low\u2010risk\/intermediate\u20101\u2010risk group (75.0% vs. 40.0%). Demethylating agent 5\u2010aza\u20102\u2032\u2010deoxycytidine treatment could partly reverse hypermethylation and, hence, restore the expression of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 gene is inactivated in <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> in part by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation, and the suppression of <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ab2 expression by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation may play a role in the development of <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12014","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T02:27:10Z","timestamp":1348540030000},"page":"469-477","source":"Crossref","is-referenced-by-count":6,"title":["Aberrant promoter methylation of <scp>D<\/scp>ab2 gene in myelodysplastic syndrome"],"prefix":"10.1111","volume":"89","author":[{"given":"Yujuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Hematology, The Sixth Hospital Shanghai Jiaotong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Sixth Hospital Shanghai Jiaotong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Sixth Hospital Shanghai Jiaotong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunkang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Sixth Hospital Shanghai Jiaotong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Sixth Hospital Shanghai Jiaotong University Shanghai 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