Document Detail

Epigenetic differences in cytogenetically normal versus abnormal acute myeloid leukemia.
MedLine Citation:
PMID:  20671427     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Methylation of tumor suppression genes (TSGs) is common in myeloid malignancies. However, application of this as a molecular marker for risk stratification in patients with AML is limited.
DESIGN AND METHODS: To elucidate the impact of patterns of TSG methylation on outcome in cytogenetically normal patients, 106 samples from patients with having normal cytogenetic AML were evaluated for methylation of 12 genes by MSP. For sake of comparison, samples from patients with AML and abnormal cytogenetics (n = 63) were also evaluated.
RESULTS: Methylation frequencies in the whole group (n = 169) were similar to previous reports for CDH1 (31%), ER (31%), FHIT (9%), p15 (INK4b) (44%), p73 (25%), and SOCS1 (75%). Methylation of CTNNA1 was observed in 10%, CEBP-α in16%, CEBP-δ in 2%, MLH1 in 24%, MGMT in 11% and DAPK in 2% of AML samples. We find that DNA methylation was more prevalent in patients with normal compared to karyotypically abnormal AML for most genes; CEBPα (20% vs 9%), CTNNA1 (14% vs 4%), and ER (41% vs 19%) (p < 0.05 for all comparisons). In contrast, p73 was more frequently methylated in patients with karyotypic abnormalities (17% vs 38%; p < 0.05), perhaps due to specific silencing of the pro-apoptotic promoter shifting p73 gene expression to the anti-apoptotic transcript. In AML patients with normal cytogenetics, TSG methylation was not associated with event free or overall survival in a multivariate analysis.
CONCLUSIONS: In patients with AML, TSG methylation is more frequent in patients with normal karyotype than those with karyotypic abnormalities but does not confer independent prognostic information for patients with normal cytogenetics.
Elizabeth A Griffiths; Steven D Gore; Craig M Hooker; Helai P Mohammad; Michael A McDevitt; B Douglas Smith; Judith E Karp; James G Herman; Hetty E Carraway
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  5     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2011-04-05     Completed Date:  2011-06-28     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  590-600     Citation Subset:  IM    
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MeSH Terms
Base Sequence
CCAAT-Enhancer-Binding Proteins / genetics
Case-Control Studies
DNA Methylation
DNA, Neoplasm / genetics
DNA-Binding Proteins / genetics
Epigenesis, Genetic*
Genes, Tumor Suppressor
HL-60 Cells
Leukemia, Myeloid, Acute / genetics*
Middle Aged
Nuclear Proteins / genetics
Receptors, Estrogen / genetics
Tumor Suppressor Proteins / genetics
U937 Cells
alpha Catenin / genetics
fms-Like Tyrosine Kinase 3 / genetics
Grant Support
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/CEBPA protein, human; 0/CTNNA1 protein, human; 0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Receptors, Estrogen; 0/Tumor Suppressor Proteins; 0/alpha Catenin; 0/tumor suppressor protein p73; EC protein, human; EC Tyrosine Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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