Hypermethylation of p15 gene associated with an inferior poor long-term outcome in childhood acute lymphoblastic leukemia.
OBJECTIVE
To quantitate methylation of the CpG island of the promoter region of the p15 gene in childhood acute lymphoblastic leukemia (ALL) and explore its effect on prognosis.


METHODS
We assessed methylation of the CpG island on the p15 gene in bone marrow mononuclear cells in 93 ALL cases and in a control group of 20 children with idiopathic thrombocytopenia (ITP) by restriction enzyme Eco52I digestion combined with polymerase chain reaction techniques. We explored the effect of varying levels of methylation on event-free survival (EFS).


RESULTS
The mean methylation level was 25 % in de novo ALL and significantly higher than the control group 2 %, P < 0.01). Forty-two percent of cases (39/93) had hypermethylation (level over 10 %). Fifty-seven percent (12/21) and 38 % (27/72) T- and precursor-B ALL patients had hypermethylation (not significant). For all patients, the 8-year EFS was (83 ± 4) %, standard risk (91 ± 4) %, intermediate risk (IR) (82 ± 5) %, and high risk (HR) (43 ± 19) % (χ(2) = 11.58, P < 0.01). Hypermethylation was associated with a lower 8-year EFS (71 ± 7 vs. 91 ± 4 %, P = 0.02) in univariate analyses.


CONCLUSIONS
Children with ALL have higher levels of p15 CpG island methylation than a control group of children with ITP. Among children with ALL, hypermethylation was associated with inferior EFS. Higher levels of p15 CpG island methylation may be a poor prognostic marker in childhood ALL.
Huirong
H
Mai
Xiaolan
X
Liu
Yixin
Y
Chen
Changgang
C
Li
Lizhi
L
Cao
Xiaowen
X
Chen
Senmin
S
Chen
Guosheng
G
Liu
Feiqiu
F
Wen
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013921:Thrombocytopenia / Q000235:genetics
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D004273:DNA, Neoplasm