Document Detail


Aberrant p15 promoter methylation in adult and childhood acute leukemias of nearly all morphologic subtypes: potential prognostic implications.
MedLine Citation:
PMID:  10706859     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. (Blood. 2000;95:1942-1949)
Authors:
I H Wong; M H Ng; D P Huang; J C Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  95     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-07     Completed Date:  2000-04-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1942-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Blotting, Southern
Cell Cycle Proteins*
Child
Child, Preschool
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Humans
Karyotyping
Leukemia / blood,  genetics*,  mortality
Leukemia, Myelomonocytic, Acute / blood,  genetics*,  mortality
Methylation
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood,  genetics*,  mortality
Prognosis
Promoter Regions, Genetic*
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Time Factors
Transcription Factors / genetics*
Tumor Suppressor Proteins*
Chemical
Reg. No./Substance:
0/CDKN2B protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Transcription Factors; 0/Tumor Suppressor Proteins
Comments/Corrections
Comment In:
Blood. 2000 Sep 1;96(5):2002   [PMID:  11041632 ]

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