Document Detail


Treatment options in advanced myelodysplastic syndrome, with emphasis on epigenetic therapy.
MedLine Citation:
PMID:  18055336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Medical management of myelodysplastic syndrome (MDS) remains challenging, particularly in advanced stages where the risk of developing acute leukemia is very high and the prospect of survival is generally poor. Over the past decade, epigenetic changes such as alterations in DNA methylation and histone modifications have been well described in MDS and are now recognized as targets of therapy (epigenetic therapy). The aim of epigenetic therapy is to reverse epigenetic changes and reactivate important genes, thereby modifying the malignant phenotype and inducing the clearance of the malignant clone via various mechanisms. Epigenetic-modifying agents may also have mechanisms of anticancer action unrelated to gene reactivation. The hypomethylating agents azacitidine and decitabine induce clinically meaningful remissions or improvements in 30% to 60% of patients with this disease, and both agents have been approved in the United States for the treatment of advanced and/or symptomatic MDS. Histone deacetylase inhibitors belong to another class of epigenetic-modifying agents that also have clinical activity in MDS. They are currently being combined with hypomethylating agents. Among other available therapeutic options, allogeneic stem cell transplantation is the only curative approach for MDS but is also characterized by significant morbidities and mortality. We review epigenetic therapy and other therapeutic approaches for patients with advanced MDS.
Authors:
Yasuhiro Oki; Jean-Pierre J Issa
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  International journal of hematology     Volume:  86     ISSN:  0925-5710     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-12-06     Completed Date:  2008-03-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  306-14     Citation Subset:  IM    
Affiliation:
Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA Modification Methylases / antagonists & inhibitors,  metabolism
Disease Progression
Epigenesis, Genetic / genetics*
Histone Deacetylase Inhibitors
Histone Deacetylases / metabolism
Humans
Myelodysplastic Syndromes / enzymology,  pathology*,  surgery,  therapy*
Stem Cell Transplantation
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; EC 2.1.1.-/DNA Modification Methylases; EC 3.5.1.98/Histone Deacetylases

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


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