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Methylation analysis of the von Hippel-Lindau gene in acute myeloid leukaemia and myelodysplastic syndromes

Leukemia volume 22, pages 1293–1295 (2008)Cite this article

DNA methylation in genomic regions called CpG islands represents an important epigenetic modification in cancer. Methylation is associated with transcriptional silencing of genes that function in cell differentiation, apoptosis, growth regulation, cell signalling and tumour invasiveness, conferring selective growth advantage to the malignant cells.1 Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) are diseases in which aberrant methylation has been described in a number of genes.2 The von Hippel-Lindau gene (VHL) is expressed in fetal and adult tissues. Expression is not restricted to the organs affected in the VHL disease, and the VHL gene is a candidate tumour suppressor. The purpose of our study was to determine whether aberrant methylation occurs in the VHL CpG island in AML and MDS.

The study population comprised 58 previously untreated patients (32 AML and 26 MDS) classified according to the WHO classification, and 10 control individuals with no haematological malignancy or solid tumour infiltration. Patients’ characteristics are shown in Table 1. The study was approved by the Institutional Review Board and by the University of Ioannina Research Committee. The presence of adequate representation of malignant cells in bone marrow samples was verified by histopathological analysis. Genomic DNA was extracted from bone marrow samples using the QIAmp DNA Minikit (Qiagen, Hilden, Germany). Bisulphite modification of genomic DNA was as described by Manning et al.3 The methylation status of the promoter region was determined using methylation-specific polymerase chain reaction (MSP) and bisulphite sequencing. MSP was performed using the primers and conditions described by Kuroki et al.4 Amplified products were resolved on 2.5% agarose gels and visualized under ultraviolet light after staining with ethidium bromide. MSP reactions were run in duplicates with positive controls (universal methylated DNA; Intergen Company, Purchase, NY, USA), negative controls from donors with no haematological malignancies and water samples with no DNA template (blanks). Primers for bisulphite sequencing were as follows:

Table 1 Characteristics of patients participating in the study
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Authors and Affiliations

  1. Department of Hematology, University Hospital of Ioannina, Ioannina, Greece

    L Benetatos, A Dasoula, E Hatzimichael & K L Bourantas

  2. Cancer Genetics and Epigenetics Laboratory, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK

    N Syed & T Crook

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  1. L Benetatos
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Correspondence to L Benetatos.

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Benetatos, L., Dasoula, A., Syed, N. et al. Methylation analysis of the von Hippel-Lindau gene in acute myeloid leukaemia and myelodysplastic syndromes. Leukemia 22, 1293–1295 (2008). https://doi.org/10.1038/sj.leu.2405053

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