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- W2058328216 abstract "The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myeloid leukemia (AML). Even though mutations have been shown to occur in MDS, a notable proportion of these affect genes involved in epigenetic maintenance, suggesting a dominant role of epigenomic dysregulation in the pathogenesis of MDS. Aberrant DNA methylation is the dominant and most well-studied epigenetic alteration in MDS. Various genes, including cell cycle regulators, apoptotic genes, and DNA repair genes, are epigenetically silenced and have roles in pathogenesis and transformation to leukemia. The involvement of these genes in MDS pathophysiology and prognosis is reviewed and reveals distinct methylation patterns between high- and low-risk subsets of this disease. Furthermore, DNA methyltransferase (DNMT) inhibitors azacitdine and decitabine are approved for treatment even though the optimal dosing strategies are still being developed. We have reviewed the mechanisms of action of these agents in MDS and show that demethylation may not correlate well with their efficacy, thus suggesting alternative modes of action. We also show that DNMT inhibitors may have potent anti-leukemic stem cell effects at lower doses and also review the mechanisms of resistance to these agents. Altogether, these studies show that even though DNA methylation has been studied extensively in MDS, its role in prognosis and response to therapy is still unclear. The use of deep sequencing and genome-wide methylome analysis will potentially uncover prognostic signatures and reveal the complexity of epigenetic dysregulation in this disease." @default.
- W2058328216 created "2016-06-24" @default.
- W2058328216 creator A5035235382 @default.
- W2058328216 creator A5039886481 @default.
- W2058328216 creator A5053377912 @default.
- W2058328216 creator A5053723355 @default.
- W2058328216 date "2013-01-01" @default.
- W2058328216 modified "2023-10-03" @default.
- W2058328216 title "Role of DNA Methylation in the Pathogenesis and Treatment of Myelodysplastic Syndromes" @default.
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