Document Detail


sFRP1 promoter methylation is associated with persistent Philadelphia chromosome in chronic myeloid leukemia.
MedLine Citation:
PMID:  19118898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epigenetic silencing of sFRP genes has been shown to lead to constitutive activation of the canonical Wnt-signaling pathway. The first description of deregulated Wnt-signaling activation in a hematological malignancy was reported in chronic myeloid leukemia (CML). To investigate whether epigenetic silencing of sFRP is responsible for the observed Wnt activation in CML, we studied the methylation and mutational status of the sFRP1 promoter in 48 chronic phase CML patients. Of the 48 CML patients 41 were shown to be unmethylated, 6 patients hemi-methylated and 1 patient fully methylated at the sFRP1 promoter. Albeit observed infrequently in chronic phase CML, sFRP1 promoter methylation correlated with primary cytogenetic resistance to imatinib mesylate. sFRP1 promoter methylation may indicate a genetically more unstable form of disease resistant to therapy and provide a key biological difference in therapy resistant patients, in addition to a possible mechanism for the observed activation of canonical Wnt signaling in CML.
Authors:
Melek Pehlivan; Zeynep Sercan; Hakki Ogun Sercan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-31
Journal Detail:
Title:  Leukemia research     Volume:  33     ISSN:  1873-5835     ISO Abbreviation:  Leuk. Res.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1062-7     Citation Subset:  IM    
Affiliation:
Department of Medical Biology and Genetics, Dokuz Eylul University, Faculty of Medicine, Inciralti, Izmir, Turkey.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Child
DNA Methylation*
Drug Resistance, Neoplasm*
Female
Gene Silencing
Humans
Intercellular Signaling Peptides and Proteins / genetics,  metabolism*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics,  metabolism*
Male
Membrane Proteins / genetics,  metabolism*
Middle Aged
Philadelphia Chromosome*
Promoter Regions, Genetic*
Signal Transduction / genetics
Wnt Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/SFRP1 protein, human; 0/Wnt Proteins

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