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Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia

Oncogene volume 22, pages 451–455 (2003)Cite this article

Abstract

Apaf-1 protein deficiency occurs in human leukaemic blasts and confers resistance to cytochrome-c-dependent apoptosis. Demethylation treatment with 5-aza-2′-deoxycytidine (5aza2dc) increased the sensitivity of the K562 leukaemic cell line to UV light-induced apoptosis in association with increased Apaf-1 protein levels. There was no correlation between Apaf-1 protein expression and Apaf-1 mRNA levels after the demethylation treatment. Methylation-specific polymerase chain reaction was used to show that the methylation can occur within the Apaf-1 promoter region in leukaemic blasts. Apaf-1 DNA methylation was demonstrated in acute myeloid leukaemia, chronic myeloid leukaemia and acute lymphoid leukaemia, suggesting that it is not specific to a particular leukaemia subtype. Apaf-1 protein expression did not correlate with Apaf-1 mRNA levels in human leukaemic blasts. Some leukaemic cells expressed high levels of Apaf-1 mRNA but low levels of Apaf-1 protein. This study suggests that Apaf-1 DNA promoter methylation might contribute to the inactivation of Apaf-1 expression. However, Apaf-1 protein levels might also be controlled at post-transcription level.

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Acknowledgements

We are pleased to acknowledge the Cancer Research UK Medical Oncology Unit for collection and storage of peripheral blood, Dr Jude Fitzgibbon for reading the manuscript, and Mr Gary Wright for helping in DNA sequencing.

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Authors and Affiliations

  1. Department of Haematology/Oncology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK

    Wei-Neng Fu, Francesco Bertoni, Stephen M Kelsey, Suzanne M McElwaine, Finbarr E Cotter, Adrian C Newland & Li Jia

  2. Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland

    Francesco Bertoni

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  1. Wei-Neng Fu
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  2. Francesco Bertoni
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Correspondence to Li Jia.

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Fu, WN., Bertoni, F., Kelsey, S. et al. Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia. Oncogene 22, 451–455 (2003). https://doi.org/10.1038/sj.onc.1206147

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