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Review

Genetic mutations in epigenetic modifiers as therapeutic targets in acute myeloid leukemia

, PhD, , PhD, , PhD, , MSc & , MD PhD (Professor)
Pages 1187-1202 | Published online: 30 May 2015
 

Abstract

Introduction: Despite enormous insights into the molecular mechanisms of acute myeloid leukemia (AML) pathophysiology, this disease is still fatal in the majority of patients, highlighting the urgent need for novel biomarkers useful in AML prognosis and therapy.

Areas covered: The advent of modern sequencing technologies has allowed the identification of genetic mutations in genes encoding for specific enzymes involved in the epigenetic regulation of gene expression. The authors review recent data demonstrating the involvement of mutations in genes encoding for epigenetic players and their complex combination with somatic genetic mutations in the pathogenesis of AML. They also discuss the prognostic and therapeutic implications of these findings.

Expert opinion: Current clinical and preclinical studies are underscoring the importance of targeting epigenetic modifiers as new biomarkers for a better prognostic risk stratification and therapeutic evaluation of intermediate-risk patients. Combining data from traditional and modern methodologies will allow a definition of the complex networks of epigenetic changes and molecular interactions between candidate epitargets and key regulators of hematopoiesis. It will thus be possible to achieve an overview of potential aberrant mechanisms driving leukemogenesis in different classes of AML patients. Such an improved approach could pave the way towards ‘personalized’ therapies.

Acknowledgments

We apologize to the authors whose work we could not cite due to reference restrictions. We wish to thank C Fisher for linguistic editing of the manuscript.

Declaration of interest

This work was supported by the EU, Blueprint project no. 282510; the Italian Flag Project CNR-EPIGEN; MIUR-PRIN-2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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