p15INK4b methylation correlates with thrombocytopenia, blast percentage, and survival in myelodysplastic syndromes in a dose dependent manner: quantitation using pyrosequencing study.
We investigated how the quantity of p15INK4b methylation related to International Prognosic Scoring System variables and survival in 74 patients with de novo myelodysplastic syndrome (MDS). Pyrosequencing of 11 consecutive CpG sites of the p15INK4b promotor region was performed, with the extent of CpG cytosine methylation assessed in terms of methylation level (MtL). Patients with >5% bone marrow blasts had higher MtL than patients with <5% blasts (10.1% vs. 6.1%, p=0.030, respectively). Methylation was not associated with chromosomal aberrations. The MtL of patients with thrombocytopenia were higher than patients without thrombocytopenia (11.2% vs. 6.2%, p=0.036, respectively); they were higher in patients with cytopenias in > or =2 lineages than in patients with either unilineage or no cytopenia (9.8% vs. 4.1%, p=0.036, respectively). The survival of patients with >7% MtL was worse than patients with <7% MtL (p=0.031). Heavy p15INK4b methylation in MDS is associated with IPSS predictors of poor prognosis and adverse survival.
Department of Laboratory Medicine, Seoul National University College of Medicine, Chongno-Gu, Seoul 110-744, South Korea.
Miyoung
M
Kim
Bora
B
Oh
Song-Yee
SY
Kim
Hyun-Kyung
HK
Park
Sang Mee
SM
Hwang
Tae Young
TY
Kim
Cha Ja
CJ
She
Inchul
I
Yang
Sung Soo
SS
Yoon
Jong Hyun
JH
Yoon
Dong Soon
DS
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000473:pathology; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012107:Research Design; D017422:Sequence Analysis, DNA / Q000379:methods*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000150:complications / Q000235:genetics*; D055815:Young Adult
D050762:Cyclin-Dependent Kinase Inhibitor p15