title: Aberrant methylation of the RIZ1 gene in myelodysplastic syndrome and acute myeloid leukemia.
abstract: We performed methylation specific PCR analysis on the RIZ1 promoter in MDS and AML. Methylation was detected in 17 of 34 MDS (50%) and 22 of 72 AML (31%) (p=0.053). Methylation was detected in eleven of 17 secondary AML from MDS (65%), and eleven of 55 de novo AML (20%) (p=0.0005). Bisulfite sequence revealed methylation at many CpG sites in the promoter. Decreased RIZ1 expression was accompanied by methylation in six of nine samples examined, while it was also observed in seven of 13 without methylation. Treatment of AML cells, that have RIZ1 methylation, with 5-Aza-dC, induced growth suppression with RIZ1 restoration. Our results suggest that the RIZ1 gene is inactivated in MDS and AML in part by methylation, whereas another mechanism should be involved in others.
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. mori@dh.twmu.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Kaori
authors.initials: K
authors.lastname: Tomita
authors.forename: Mari
authors.initials: M
authors.lastname: Ohwashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kondoh
authors.forename: Hanae
authors.initials: H
authors.lastname: Shimura
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiseki
authors.forename: Michiko
authors.initials: M
authors.lastname: Okada
authors.forename: Toshiko
authors.initials: T
authors.lastname: Motoji
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D020298:U937 Cells; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000077209:Decitabine; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human; D001374:Azacitidine