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A somatic EZH2 mutation in childhood acute myeloid leukemia

Leukemia volume 26, pages 1701–1703 (2012)Cite this article

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Although treatment results in childhood acute myeloid leukemia (AML) have improved with the use of risk-directed treatment and improved supportive care, there is still a significant number of patients with unfavorable prognosis.1 To date, analyses of cytogenetic aberrations provide the most important prognostic information at diagnosis of this heterogeneous disease. Different mutations in several genes have been identified in childhood AML, most commonly NPM1, FLT3-ITD, CEBPA and WT1.1 Some of these genetic alterations have been associated with treatment outcome and may serve as a basis for improved risk assessment and molecular-based therapies. Recently, mutations in genes that are involved in epigenetic regulation have been described in pediatric AML including TET2, DNMT3A and IDH1/2.2, 3, 4, 5, 6

There is growing evidence that epigenetic deregulation has an important role in the pathogenesis of childhood and adult AML. The most common chromosomal abnormalities found in childhood AML cause chromatin changes through rearrangement of the MLL gene—a histone methyltransferase—to several partner genes.1 Besides histone modifications, changes in DNA methylation can also be observed. Using large-scale genome-wide DNA methylation profiling, Figueroa et al.7 recently revealed specific DNA methylation signatures for identification of biologically distinct AML subtypes in adults. Moreover, an AML subset characterized by hypermethylation and silencing of the CEBPA promoter has been shown to cause similar expression profiles as an AML subtype with CEBPA mutations.8

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Acknowledgements

We greatly appreciate the information retrieval and data analysis services of Ilona Wolff. The excellent technical assistance of Anja Waldau, Susan Wittig and Nadine Pfaffendorf-Regler is gratefully acknowledged.

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Authors and Affiliations

  1. Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    T Ernst, A Pflug, J Rinke & A Hochhaus

  2. Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Jena, Germany

    J Ernst, J F Beck & B Gruhn

  3. Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Leipzig, Leipzig, Germany

    U Bierbach

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Correspondence to T Ernst.

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Ernst, T., Pflug, A., Rinke, J. et al. A somatic EZH2 mutation in childhood acute myeloid leukemia. Leukemia 26, 1701–1703 (2012). https://doi.org/10.1038/leu.2012.16

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