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Global increase in DNA methylation in patients with myelodysplastic syndrome

Leukemia volume 22, pages 1954–1956 (2008)Cite this article

Epigenetic aberrations are now well recognized as very frequent and also as early events in the process of malignant transformation. It is very often reported that gene-specific hypermethylation occurs in the context of global hypomethylation.1 Accordingly, experimentally induced reduction of global methylation levels increases tumour formation in mice under certain circumstances.2 Somewhat contradictory, in patients with myelodysplastic syndrome (MDS), the induction of hypomethylation using DNA methyltransferase inhibitors leads to very promising clinical response rates and haematological improvement.3 Therefore, we analysed the global methylation level in a large cohort of MDS patients comprising all subgroups (n=127), to figure out the molecular mechanisms underlying this unexpected finding. Results were compared to an age-matched control group of healthy subjects (n=26; see Table 1). All samples were retrieved and processed following the guidelines of the local Ethics Committee.

Table 1 Patient data
Full size table

Mononuclear cells were isolated from bone marrow aspirates and the global DNA methylation level was assessed using two completely independent methods. First, the methylation level of the highly repetitive LINE-1 sequence element, which is scattered throughout the human genome, was measured employing Pyrosequencing technology. The methylation status of this highly repetitive element is a good surrogate marker for global methylation level.4 Second, the incorporation of nucleotides after methylation-sensitive digestion of genomic DNA was determined. The amount of nucleotides incorporated depends on the fraction of restriction enzyme recognition sites blocked by cytosine methylation and is a direct measure of the methylation status of the human genome.5 In addition, for 12 patient samples and 2 controls, sufficient genomic DNA was available for methylation analysis by Southern blotting with a LINE-1 probe, the gold standard for detection of hypomethylation for many years.

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Acknowledgements

This study was supported by a grant from the Deutsche Krebshilfe, Dr Mildred Scheel Stiftung (to UL and HK).

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Authors and Affiliations

  1. Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany

    D Römermann, B Hasemeier, K Metzig, F Länger, H Kreipe & U Lehmann

  2. Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover, Hannover, Germany

    G Göhring & B Schlegelberger

Authors
  1. D Römermann
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  2. B Hasemeier
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  3. K Metzig
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  4. G Göhring
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  5. B Schlegelberger
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  6. F Länger
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  7. H Kreipe
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  8. U Lehmann
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Correspondence to U Lehmann.

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Römermann, D., Hasemeier, B., Metzig, K. et al. Global increase in DNA methylation in patients with myelodysplastic syndrome. Leukemia 22, 1954–1956 (2008). https://doi.org/10.1038/leu.2008.76

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