{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:01:31Z","timestamp":1790413291183,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":353,"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":[[2001,1]]},"abstract":"<jats:p>To investigate the time sequence of occurrence of <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> gene methylation in myelodysplastic syndrome (MDS) and its correlation with leukaemic transformation and survival of patients, the methylation status of the <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> promoter region was analysed in 50 patients and was serially studied in 22 of them. Of the 50 patients, 17 (34%) showed <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> gene methylation, first demonstrated at diagnosis or during follow\u2010up. When FAB subtypes at the time of study were used in the analysis, the incidence of <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> methylation in each risk group of MDS remained stable throughout the course: 0% for low\u2010risk MDS [refractory anaemia (RA) and RA with ring sideroblasts] and from 23% at diagnosis to 30% for high\u2010risk MDS [RA with excess of blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia] respectively. The incidence of <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> methylation rose to 60% at initial study and, finally, to 75% in cases of acute myeloid leukaemia (AML) evolved from MDS. Most patients (69%) with <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> methylation showed disease progression to AML; it could be detected before, at the time or after the diagnosis of leukaemic transformation. <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> methylation in MDS patients implicated a shorter survival time in univariate analyses, but its prognostic significance disappeared in multivariate analyses. In conclusion, <jats:italic>p15<\/jats:italic><jats:sup><jats:italic>INK4B<\/jats:italic><\/jats:sup> methylation can be detected early at the diagnosis of MDS or acquired during disease progression. It may play an important role in the pathogenesis of some high\u2010risk MDS and is related to leukaemic transformation of MDS.<\/jats:p>","DOI":"10.1046\/j.1365-2141.2001.02496.x","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:10:00Z","timestamp":1027678200000},"page":"148-154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Methylation of the <i>p15<\/i><sup><i>INK4B<\/i><\/sup> gene in myelodysplastic syndrome: it can be detected early at diagnosis or during disease progression and is highly associated with leukaemic transformation"],"prefix":"10.1111","volume":"112","author":[{"given":"Hwei\u2010Fang","family":"Tien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih\u2010Luh","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woei","family":"Tsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Chi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenn\u2010Yu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu\u2010Hwa","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Chang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Ching","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,20]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"832","article-title":"Frequent 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