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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 1942-1949
Aberrant p15 promoter methylation in adult and childhood
acute leukemias of nearly all morphologic subtypes: potential
prognostic implications
Ivy H. N. Wong,
Margaret H. L. Ng,
Dolly P. Huang, and
Joseph C. K. Lee
From the Department of Anatomical and Cellular Pathology, Prince of
Wales Hospital, Chinese University of Hong Kong, Hong Kong.
We prospectively analyzed p15 and p16 promoter
methylation patterns using methylation-specific polymerase chain
reaction (PCR) in patients with adult and childhood acute leukemias and
studied the association of methylation patterns with chromosomal
abnormalities and prognostic variables. In nearly all
French-American-British leukemia subtypes, we found p15
methylation in bone marrow or peripheral blood cells from 58% (46/79)
of patients with acute myeloid leukemia (AML), acute lymphoblastic
leukemia (ALL), or acute biphenotypic leukemia (ABL). An identical
alteration was detected in blood plasma from 11 of 12 of these patients
(92%). We also demonstrated for the first time concomitant p16
and p15 methylation in 22% (8/37) of adults with AML or ALL,
exclusively in those with M2, M4, or L2 subtypes. According to
cytogenetic data from 35 patients with ALL, AML, or ABL, 82% (14/17)
of those with unmethylated p15 alleles had normal karyotypes or
hyperdiploidies associated with a favorable prognosis. Conversely, 44%
(8/18) of patients with p15 methylation had chromosomal
translocations, inversions, or deletions, suggesting an interplay of
these abnormalities with p15 methylation. As a prognostic
marker for disease monitoring, p15 methylation appears to be
more widely applicable than BCR-ABL, AF4-MLL, and
AML1-ETO transcripts, which were detectable in only 8% (4/48)
of patients by reverse transcriptase-PCR. Thirty-nine of 43 blood
samples (91%) sequentially collected from 12 patients with AML, ALL,
or ABL showed p15 methylation status in excellent concordance
with morphologic disease stage. Early detection of p15
methylation at apparent remission or its acquisition during follow-up
may prove valuable for predicting relapse. Overall survival of patients
with p15 methylation was notably shortened among 38 adults with
AML and 12 adults with ALL. Aberrant p15 methylation may have
important prognostic implications for clinical monitoring and
risk assessment.
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Related Letter in Blood Online:
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Anticorresponding p15 promoter methylation and microsatellite instability in acute myeloblastic leukemia
- Emma P. Das-Gupta and Nigel H. Russell
Blood 2000 96: 2002.
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