Aberrant methylation of the RIZ1 gene in myelodysplastic syndrome and acute myeloid leukemia.
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.
Mori
Naoki
N
Department of Hematology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. mori@dh.twmu.ac.jp
Yoshinaga
Kentaro
K
Tomita
Kaori
K
Ohwashi
Mari
M
Kondoh
Toshiaki
T
Shimura
Hanae
H
Wang
Yan-Hua
YH
Shiseki
Masayuki
M
Okada
Michiko
M
Motoji
Toshiko
T
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
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