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  • Spotlight Review
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Spotlight on Epigenetics in Hematologic Malignancies

Origins of aberrant DNA methylation in acute myeloid leukemia

Leukemia volume 28, pages 1–14 (2014)Cite this article

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Abstract

Aberrant DNA methylation patterns are a characteristic feature of cancer including myeloid malignancies such as acute myeloid leukemia (AML). The mechanisms behind aberrant DNA methylation have long remained obscure. New genome-wide studies have elucidated the genome and epigenome of solid tumors and AML. Molecular subtypes of AML were found to exhibit highly distinct DNA methylation profiles. Clonal evolution patterns of AML were recently dissected and might shape epigenetic dysregulation. Also, recurrent mutations in epigenetic modifying enzymes were identified in AML and linked to distinct DNA methylation signatures. The genetic background, thus, takes center stage as a driver of epigenetic dysregulation in AML. First mechanistic insights into the dysregulation of DNA methylation by recurrent mutations have already been gained. Other studies suggest that epigenomic plasticity and aging-associated changes in DNA methylation also contribute extensively to aberrant DNA methylation in cancer. Epigenetic dysregulation, therefore, seems to also occur independently of the genetic background. Furthermore, global changes in chromatin conformation and nuclear organization have also been proposed as potential contributors to aberrant DNA methylation. This review will summarize and discuss current concepts regarding the mechanisms behind aberrant DNA methylation in cancer and specifically AML.

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Acknowledgements

We are grateful to members of the Müller-Tidow lab and to Frank Rosenbauer for helpful comments and critical discussions. We apologize to all colleagues whose work could not be cited due to space restrictions. Work on epigenetics or AML in our lab are supported by the Deutsche Forschungsgemeinschaft (SPP1463-MU 1328/9-1, SFB1009A07), the Deutsche Krebshilfe (110807), the José-Carreras Leukämiestiftung (R10/35f), the Else-Kröner Fresenius Stiftung (2012_A76) and the Innovative Medizinische Forschung at the University of Münster (I-BÄ111116).

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  1. Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany

    T Schoofs, W E Berdel & C Müller-Tidow

  2. Interdisciplinary Centre for Clinical Research (IZKF) at the University of Muenster, Muenster, Germany

    C Müller-Tidow

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  1. T Schoofs
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  2. W E Berdel
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Correspondence to C Müller-Tidow.

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Schoofs, T., Berdel, W. & Müller-Tidow, C. Origins of aberrant DNA methylation in acute myeloid leukemia. Leukemia 28, 1–14 (2014). https://doi.org/10.1038/leu.2013.242

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