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Acute Leukemias

Expression of myeloperoxidase in acute myeloid leukemia blasts mirrors the distinct DNA methylation pattern involving the downregulation of DNA methyltransferase DNMT3B

Leukemia volume 28, pages 1459–1466 (2014)Cite this article

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Abstract

Myeloperoxidase (MPO) has been associated with both a myeloid lineage commitment and favorable prognosis in patients with acute myeloid leukemia (AML). DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. Therefore, MPO gene transcription was directly and indirectly regulated by DNA methylation. A DNA methylation microarray subsequently revealed a distinct methylation pattern in 33 genes, including DNA methyltransferase 3 beta (DNMT3B), in CD34-positive cells obtained from AML patients with a high percentage of MPO-positive blasts. Based on the inverse relationship between the methylation status of DNMT3B and MPO, we found an inverse relationship between DNMT3B and MPO transcription levels in CD34-positive AML cells (P=0.0283). In addition, a distinct methylation pattern was observed in five genes related to myeloid differentiation or therapeutic sensitivity in CD34-positive cells from AML patients with a high percentage of MPO-positive blasts. Taken together, the results of the present study indicate that MPO may serve as an informative marker for identifying a distinct and crucial DNA methylation profile in CD34-positive AML cells.

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Acknowledgements

We thank Ms M Yamaguchi and Ms H Urakami for their technical assistance. This work was partly supported by the grant from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Hematology, Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    H Itonaga, D Imanishi, K Ando, Y Sawayama, Y Imaizumi, J Taguchi, T Hata & Y Miyazaki

  2. Department of Hematology, Sasebo City General Hospital, Sasebo, Japan

    H Itonaga, S Sato, H Tsushima & Y Moriuchi

  3. Laboratory for Stem Cell Biology, RIKEN Center for Development Biology, Kobe, Japan

    Y-F Wong

  4. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    D Sasaki, K Tsuruda, H Hasegawa & K Yanagihara

  5. Department of Internal Medicine, National Hospital Organization Nagasaki Medical Center, Ohmura, Japan

    S Yoshida

  6. School of Health Sciences, University of the Ryukyus, Nishihara, Japan

    T Fukushima

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  1. H Itonaga
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Author contributions

HI and Y Miyazaki conceived and designed the study; HI, DI, WYF, SS, KA, YS, DS, KT, HH, YI, JT, HT, SY, TF, TH, Y Moriuchi, KY and Y Miyazaki collected and analyzed the samples and data; HI and Y Miyazaki performed the statistical analysis, wrote the manuscript and created the figures and tables; and all authors critically reviewed the manuscript and read and approved the final version.

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Itonaga, H., Imanishi, D., Wong, YF. et al. Expression of myeloperoxidase in acute myeloid leukemia blasts mirrors the distinct DNA methylation pattern involving the downregulation of DNA methyltransferase DNMT3B. Leukemia 28, 1459–1466 (2014). https://doi.org/10.1038/leu.2014.15

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