Document Detail


Expression of IGFBP7 in acute leukemia is regulated by DNA methylation.
MedLine Citation:
PMID:  21040219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The important role of insulin-like growth factor binding protein 7 (IGFBP7) as a tumor suppressor in solid tumors has been revealed in several studies. Interestingly, in a recent study IGFBP7 was also shown to be aberrantly expressed in acute leukemia. Moreover, in acute T-lymphoblastic leukemia (T-ALL), high IGFBP7 expression predicts primary therapy resistance. In order to elucidate the mechanisms underlying aberrant IGFBP7 expression, we used pyrosequencing technology to investigate the DNA methylation of IGFBP7 in 109 T-ALL patient samples. Aberrant methylation was shown and hypomethylation was associated with an early immunophenotype and co-expression of the stem cell markers CD117 (P < 0.001) and CD34 (P < 0.001). In concordance, gene expression profiles of 86 T-ALL patients revealed upregulation of stem cell markers (CD34 and CD133) as well as genes associated with poor outcome and pathogenesis of leukemia (MN1, BAALC, FLT3) in the high IGFBP7 expression group. In conclusion, aberrant IGFBP7 expression is regulated by DNA methylation in acute leukemia. Hypomethylation of the gene is likely to characterize an immature and a more malignant subtype of the disease.
Authors:
Sandra Heesch; Isabelle Bartram; Martin Neumann; Jana Reins; Maximilian Mossner; Cornelia Schlee; Andrea Stroux; Torsten Haferlach; Nicola Goekbuget; Dieter Hoelzer; Wolf-Karsten Hofmann; Eckhard Thiel; Claudia D Baldus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-29
Journal Detail:
Title:  Cancer science     Volume:  102     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  253-9     Citation Subset:  IM    
Copyright Information:
© 2010 Japanese Cancer Association.
Affiliation:
Department of Hematology and Oncology, Campus Benjamin Franklin, Charité, University Hospital Berlin, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
DNA Methylation*
Female
Gene Expression Profiling
Humans
Insulin-Like Growth Factor Binding Proteins / genetics*
Male
Middle Aged
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  metabolism
RNA, Messenger / analysis
Chemical
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Proteins; 0/RNA, Messenger; 0/insulin-like growth factor binding protein-related protein 1

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


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