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DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia

Leukemia volume 26, pages 1106–1107 (2012)Cite this article

Acute myeloid leukemia (AML) is a disease of the elderly, affecting patients with a median age of 65–70 years. Cytotoxic chemotherapy remains the mainstay of treatment in younger patients (often defined as those below the age of 60 years), but is associated with lower complete remission (CR) rates and greater toxicity in older patients (⩾60 years), resulting in poor long-term outcomes and a median overall survival (OS) of <1 year.1 Thus, there is a need for novel, effective and well-tolerated treatment approaches, especially for older patients.

Epigenetic changes, including aberrant DNA methylation, can result in silencing of tumor suppressor genes and likely contribute to the pathogenesis of AML.2 Aberrant DNA methylation can be reversed pharmacologically by inhibitors of DNA methyltransferase (DNMT) enzymes.2 Two azanucleotide DNMT inhibitors, azacitidine and decitabine, are approved for the treatment of patients with myelodysplastic syndromes, and are also being studied in AML.3 Our group has recently reported promising results with a well-tolerated 10-day schedule of low-dose decitabine, including a CR rate of 47% and a median OS of 1 year in older patients with untreated AML who were considered unfit for or refused intensive chemotherapy.4

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Authors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    K H Metzeler, A Walker, S Geyer, R Garzon, R B Klisovic, C D Bloomfield, W Blum & G Marcucci

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  1. K H Metzeler
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  2. A Walker
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  3. S Geyer
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  4. R Garzon
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  5. R B Klisovic
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  6. C D Bloomfield
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  7. W Blum
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  8. G Marcucci
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Correspondence to G Marcucci.

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Metzeler, K., Walker, A., Geyer, S. et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia 26, 1106–1107 (2012). https://doi.org/10.1038/leu.2011.342

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