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Updates on DNA methylation modifiers in acute myeloid leukemia

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Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Chemotherapy with cytotoxic agents is the standard of care, but is associated with a high rate of adverse events. Elderly patients are frequently intolerant to such treatment, presenting a very poor prognosis. The hypomethylating agents (HMA) azacitidine or decitabine represent one of the main therapeutic alternatives for these patients. Isocitrate dehydrogenase inhibitors (IDH) constitute another therapeutic class with DNA methylation effects in AML. In this article, we review the use of first- and second-generation HMA and IDH inhibitors in AML. The data collected demonstrated that HMA are generally considered effective and safe for AML patients who are not eligible for standard chemotherapy. The combination of azacitidine or decitabine with venetoclax was recently approved by the US Food and Drug Administration (FDA) for older AML patients and those unfit for intense chemotherapy. IDH inhibitors also showed encouraging results for relapsed/refractory AML patients harboring an IDH mutation and received FDA approval. Therefore, recent studies have led to the emergence of new therapeutic options using HMA and IDH inhibitors for specific groups of AML patients, representing an important step in the treatment of this aggressive malignancy. New options should emerge from the ongoing studies in the coming years.

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Acknowledgments

The authors would like to thank Prof Fernando Luiz Affonso Fonseca for valuable discussions.

Funding

Mariana Lazarini gratefully acknowledges funding support from São Paulo Research Foundation, research grant 17/19674–2.

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Bruna Contieri declares she has no conflicts of interest. Bruno Kosa Lino Duarte declares he has no conflicts of interest. Mariana Lazarini declares she has no conflicts of interest.

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Contieri, B., Duarte, B.K.L. & Lazarini, M. Updates on DNA methylation modifiers in acute myeloid leukemia. Ann Hematol 99, 693–701 (2020). https://doi.org/10.1007/s00277-020-03938-2

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