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Review
. 2010 Apr;24(2):317-30.
doi: 10.1016/j.hoc.2010.02.007.

Epigenetic changes in the myelodysplastic syndrome

Jean-Pierre Issa  1
Affiliations
Review

Epigenetic changes in the myelodysplastic syndrome

Jean-Pierre Issa. Hematol Oncol Clin North Am. 2010 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Two silencing pathways. Left: Model of the DNA methylation associated gene silencing loop. The cascade of events may start with DNA methylation triggering histone modifications or with Histone H3 lysine 9 (K9) methylation triggering silencing, which then promotes DNA methylation. Right: Polycomb group (PcG) based silencing. Targeting PRC2 to a given promoter results in histone deacetylation and H3K27 trimethylation, which triggers PRC1 binding, a closed chromatin structure and gene silencing. In turn, H3K27 trimethylation may also recruit PRC2 binding to sustain silencing through mitosis.
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References

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