Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-06-12

AUTHORS

E H Estey

ABSTRACT

Randomized trials have clearly demonstrated that the hypomethylating agents azacitidine and decitabine are more effective than ‘best supportive care’(BSC) in reducing transfusion frequency in ‘low-risk’ myelodysplasia (MDS) and in prolonging survival compared with BSC or low-dose ara-C in ‘high-risk’ MDS or acute myeloid leukemia (AML) with 21–30% blasts. They also appear equivalent to conventional induction chemotherapy in AML with >20% blasts and as conditioning regimens before allogeneic transplant (hematopoietic cell transplant, HCT) in MDS. Although azacitidine or decitabine are thus the standard to which newer therapies should be compared, here we discuss whether the improvement they afford in overall survival is sufficient to warrant a designation as a standard in treating individual patients. We also discuss pre- and post-treatment covariates, including assays of methylation to predict response, different schedules of administration, combinations with other active agents and use in settings other than active disease, in particular post HCT. We note that rational development of this class of drugs awaits delineation of how much of their undoubted effect in fact results from hypomethylation and reactivation of gene expression. More... »

PAGES

1803-1812

References to SciGraph publications

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  • 2009-02-05. The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells in LEUKEMIA
  • 2009-10-04. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction in NATURE GENETICS
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  • 2007-12-13. A prognostic score for patients with lower risk myelodysplastic syndrome in LEUKEMIA
  • 2013-01-14. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation in LEUKEMIA
  • 2013-03-01. Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation in LEUKEMIA
  • 2012-06-05. Fas expression at diagnosis as a biomarker of azacitidine activity in high-risk MDS and secondary AML in LEUKEMIA
  • 2012-06-05. A randomized study of decitabine versus conventional care for maintenance therapy in patients with acute myeloid leukemia in complete remission in LEUKEMIA
  • 2011-04-15. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias in LEUKEMIA
  • 2011-11-29. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia in LEUKEMIA
  • 2011-03-07. Cancer epigenetics reaches mainstream oncology in NATURE MEDICINE
  • 2013-01-28. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study in LEUKEMIA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2013.173

    DOI

    http://dx.doi.org/10.1038/leu.2013.173

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1047612708

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23757301


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