Promoter hypermethylation plays an important
role in the inactivation of cancerrelated
genes. This abnormality occurs
early in leukemogenesis and seems to be
associated with poor prognosis in acute
lymphoblastic leukemia (ALL). To determine
the extent of hypermethylation in
ALL, we analyzed the methylation status
of the CDH1, p73, p16, p15, p57, NES-1,
DKK-3, CDH13, p14, TMS-1, APAF-1,
DAPK, PARKIN, LATS-1, and PTEN genes
in 251 consecutive ALL patients.Atotal of
77.3% of samples had at least 1 gene
methylated, whereas 35.9% of cases had
4 or more genes methylated. Clinical features
and complete remission rate did not
differ among patients without methylated
genes, patients with 1 to 3 methylated
genes (methylated group A), or patients
with more than 3 methylated genes (methylated
group B). Estimated disease-free
survival (DFS) and overall survival (OS) at
11 years were 75.5% and 66.1%, respectively,
for the nonmethylated group; 37.2%
and 45.5% for methylated group A; and
9.4% and 7.8% for methylated group B
(P < .0001 and P .0004, respectively).
Multivariate analysis demonstrated that
the methylation profile was an independent
prognostic factor in predicting DFS
(P < .0001) and OS (P .003). Our results
suggest that the methylation profile may
be a potential new biomarker of risk prediction
in AL