title: Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia.
abstract: Aberrant DNA methylation is frequently observed in adults with myelodysplastic syndrome (MDS), and is recognized as a critical event in the disease's pathogenesis and progression. This is the first report to investigate the methylation status of p15 and p16, cell cycle regulatory genes, in children with MDS (n = 9) and juvenile myelomonocytic leukaemia (JMML; n = 18) by using a methylation-specific polymerase chain reaction. The frequency of p15 hypermethylation in paediatric MDS was 78% (7/9), which was comparable to that in adult MDS. In contrast, p15 hypermethylation in JMML was a rare event (17%; 3/18). In JMML, clinical and laboratory characteristics including PTPN11 mutations and aberrant colony formation were not different between the three patients with hypermethylated p15 and the others. Aberrant methylation of p16 was not detected in children with either MDS or JMML. Since p15 and p16 genes were unmethylated in two children with JMML, in whom the disease had progressed with an increased number of blasts, a condition referred to as blastic crisis, we infer that the aberrant methylation of these genes is not responsible for the progression of JMML. The results suggest that demethylating agents may be effective in most children with MDS and a few patients with JMML.
authors.affiliation: Department of Paediatric Haematology-Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Takeo
authors.initials: T
authors.lastname: Kubota
authors.forename: Hirohide
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Imiko
authors.initials: I
authors.lastname: Hirose
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tsuruta
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ebihara
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Zhao
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakashita
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
authors.forename: Mariko
authors.initials: M
authors.lastname: Isomura
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Akinori
authors.initials: A
authors.lastname: Hoshika
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Tsuji
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases