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  • Spotlight Review
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Spotlight on Epigenetics in Hematologic Malignancies

Epigenetics of myelodysplastic syndromes

Leukemia volume 28, pages 497–506 (2014)Cite this article

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Abstract

Myelodysplastic syndromes (MDS) are clonal diseases of the elderly characterized by chronic cytopenias, dysplasia and a variable risk of progression to acute myeloid leukemia (AML). Aberrant methylation of tumor-suppressor gene promoters has been established for many years and recently tracked to the most immature cells of MDS, suggesting that these alterations are drivers of MDS pathogenesis. In recent years, recurrent somatic mutations in genes encoding proteins involved in DNA methylation and demethylation and in covalent histone modifications have been reported in myeloid malignancies, including MDS. Whole-genome epigenetic profiles of MDS are also emerging. In parallel with these advances in the molecular pathogenesis of MDS, clinical trials have established hypomethylating agents (HMAs) as the mainstay of therapy in the advanced forms of the disease. In this review, we summarize the current understanding of the molecular machinery involved in epigenetic regulation, discuss how epigenetic alterations arise in MDS and contribute to its pathogenesis and then discuss the mode of action of HMAs in MDS.

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Acknowledgements

We apologize to the many original contributions in the field that could not be cited due to manuscript limitations. We are indebted to Eric Solary for critical review of the manuscript.

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  1. Hematology Department, Hopital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France

    R Itzykson & P Fenaux

  2. Université Paris Diderot (Paris 7), Paris, France

    R Itzykson & P Fenaux

  3. INSERM U944, Paris, France

    R Itzykson

  4. INSERM UMR-S-940, Paris, France

    P Fenaux

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Itzykson, R., Fenaux, P. Epigenetics of myelodysplastic syndromes. Leukemia 28, 497–506 (2014). https://doi.org/10.1038/leu.2013.343

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