{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:32:46Z","timestamp":1760707966860},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T00:00:00Z","timestamp":1218067200000},"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":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bone morphogenetic proteins (BMP), belonging to the transforming growth factor\u2010\u03b2 superfamily, are multifunctional regulators of cell proliferation, differentiation and apoptosis in various types of malignant cells. In this study, we investigated <jats:italic>BMP\u20106<\/jats:italic> promoter methylation in patients with various types of leukemias. The <jats:italic>BMP\u20106<\/jats:italic> methylation was found preferentially in adult T\u2010cell leukemia (ATL) (49 of 60, 82%) compared with other types of leukemias studied including acute myeloid leukemia (3 of 67, 5%), acute lymphoblastic leukemia (6 of 38, 16%) and chronic lymphocytic leukemia (1 of 21, 5%). Among subtypes of ATL, the <jats:italic>BMP\u20106<\/jats:italic> gene was more frequently methylated in aggressive ATL forms of acute (96%) and lymphoma (94%) types than less malignant chronic ATL (44%) and smoldering ATL (20%). We also analyzed the methylation status of peripheral blood mononuclear cells from healthy donors and nonmalignant lymph nodes with reactive lymphadenopathy, none of which showed detectable <jats:italic>BMP\u20106<\/jats:italic> methylation in this study. The <jats:italic>BMP\u20106<\/jats:italic> methyaltion was correlated with decreased mRNA transcript and protein expression. Expression of <jats:italic>BMP\u20106<\/jats:italic> was restored by the demethylating agent 5\u2010aza\u20102\u2032\u2010deoxycytidine, suggesting that methylation was associated with the transcriptional silencing. Serial analysis demonstrated an increasing methylation of CpG sites in the <jats:italic>BMP\u20106<\/jats:italic> promoter and the resultant suppression of <jats:italic>BMP\u20106<\/jats:italic> expression as ATL progressed. These findings suggested that <jats:italic>BMP\u20106<\/jats:italic> promoter methylation is likely to be a common epigenetic event at later stages of ATL and that the methylation profiles may be useful for the staging of ATL as well as for evaluation of the individual risk of developing the disease. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23749","type":"journal-article","created":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T19:33:20Z","timestamp":1218137600000},"page":"1824-1831","source":"Crossref","is-referenced-by-count":23,"title":["Promoter methylation of the bone morphogenetic protein\u20106 gene in association with adult T\u2010cell 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