Document Detail


C/EBPA gene mutation and C/EBPA promoter hypermethylation in acute myeloid leukemia with normal cytogenetics.
MedLine Citation:
PMID:  20513120     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the current study, we investigated C/EBPA gene mutations and promoter hypermethylation in a series of 53 patients with CN-AML. In addition, we also analyzed two other frequent mutations (FLT3/ITD and NPM1) in these patients and correlated them with C/EBPA gene alterations. 13/53 patients were FLT3/ITD+/NPM1-, 11/53 patients were FLT3/ITD+/NPM1+, 9/53 patients were FLT3/ITD-/NPM1+, and 20/53 patients were FLT3/ITD-/NPM1-. Four of 53 cases displayed C/EBPA mutations, whereas 49 cases had only C/EBPA wild-type alleles. Of the four positive cases, three patients had N-terminal mutations only, whereas one patient had mutations in both the N- and C-terminal region. Two of the four positive cases also harbored both FLT3/ITD and NPM1 mutation simultaneously, whereas the other two patients had neither FLT3/ITD nor NPM1 mutations. Furthermore, 7/53 cases displayed C/EBPA promoter hypermethylation. Interestingly, they were all in CN-AML cases without FLT3/ITD or NPM1 mutations. None of the seven patients with C/EBPA promoter hypermethylation showed C/EBPA mutation. In conclusion, C/EBPA mutation and promoter hypermethylation can be detected at a relatively low frequency in de novo CN-AML patients, suggesting they may contribute to leukemogenesis. C/EBPA mutation appears to be seen in "high-risk" AML (FLT3/ITD+/NPM1+; FLT3/ITD+/NPM1- or FLT3/ITD-/NPM1-), while C/EBPA hypermethylation appears to be more common in AML with FLT3/ITD- /NPM1- and is not associated with C/EBPA mutation.
Authors:
Ying Lu; Wengang Chen; Wei Chen; Anthony Stein; Lawrence M Weiss; Qin Huang
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of hematology     Volume:  85     ISSN:  1096-8652     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-06-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  426-30     Citation Subset:  IM    
Copyright Information:
2010 Wiley-Liss, Inc.
Affiliation:
Department of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Aged
CCAAT-Enhancer-Binding Proteins / genetics*
Cell Transformation, Neoplastic / genetics
DNA Methylation*
DNA Mutational Analysis
Female
Humans
Leukemia, Myeloid / genetics*
Male
Middle Aged
Nuclear Proteins / genetics
Promoter Regions, Genetic / genetics*
Risk
Young Adult
fms-Like Tyrosine Kinase 3 / genetics
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/CEBPA protein, human; 0/Nuclear Proteins; 117896-08-9/nucleophosmin; EC 2.7.10.1/FLT3 protein, human; EC 2.7.10.1/fms-Like Tyrosine Kinase 3

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


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