Document Detail


Epigenetic changes in the myelodysplastic syndrome.
MedLine Citation:
PMID:  20359628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epigenetic mechanisms, such as DNA methylation and histone modifications, drive stable, clonally propagated changes in gene expression and can therefore serve as molecular mediators of pathway dysfunction in neoplasia. Myelodysplastic syndrome (MDS) is characterized by frequent epigenetic abnormalities, including the hypermethylation of genes that control proliferation, adhesion, and other characteristic features of this leukemia. Aberrant DNA hypermethylation is associated with a poor prognosis in MDS that can be accounted for by more rapid progression to acute myeloid leukemia. In turn, treatment with drugs that modify epigenetic pathways (DNA methylation and histone deacetylation inhibitors) induces durable remissions and prolongs life in MDS, offering some hope and direction in the future management of this deadly disease.
Authors:
Jean-Pierre Issa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Hematology/oncology clinics of North America     Volume:  24     ISSN:  1558-1977     ISO Abbreviation:  Hematol. Oncol. Clin. North Am.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-02     Completed Date:  2010-06-17     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  8709473     Medline TA:  Hematol Oncol Clin North Am     Country:  United States    
Other Details:
Languages:  eng     Pagination:  317-30     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA. jpissa@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Acetylation / drug effects
Acute Disease
Azacitidine / analogs & derivatives,  therapeutic use
Cell Transformation, Neoplastic / drug effects
DNA Methylation / drug effects
Epigenesis, Genetic* / drug effects
Histone Deacetylase Inhibitors / therapeutic use
Histone Deacetylases / physiology
Histones / metabolism
Humans
Leukemia, Myeloid / etiology,  prevention & control
Methylation
Myelodysplastic Syndromes / drug therapy,  genetics*
Neoplasms / genetics,  metabolism
Protein Processing, Post-Translational / drug effects
Grant Support
ID/Acronym/Agency:
CA098006/CA/NCI NIH HHS; CA100632/CA/NCI NIH HHS; CA121104/CA/NCI NIH HHS; P01 CA108631-050003/CA/NCI NIH HHS; P50 CA100632-010001/CA/NCI NIH HHS; P50 CA100632-060001/CA/NCI NIH HHS; P50 CA100632-06S1/CA/NCI NIH HHS; R01 CA121104-03/CA/NCI NIH HHS; R01 CA121104-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Histones; 2353-33-5/decitabine; 320-67-2/Azacitidine; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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