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Aberrant methylation and impaired expression of the p15INK4b cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML)

Leukemia volume 17, pages 910–918 (2003)Cite this article

Abstract

The important cell cycle regulatory gene p15INK4b has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15INK4b gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5′ region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.

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Acknowledgements

We thank Britta Hasemeier for expert assistance in preparing the figures as well as Henriette Bruchhardt and Reinhard von Wasielewski for assistance and advice, respectively, concerning the immunohistochemical detection of the p15INK4b protein. Grant numbers and sources of support: Deutsche Krebshilfe, Grant 10-1842-Le I.

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Authors and Affiliations

  1. Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Street 1, Hannover, Germany

    M Tessema, F Länger, J Dingemann, H Kreipe & U Lehmann

  2. Department of Hematology/Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Street 1, Hannover, Germany

    A Ganser

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  1. M Tessema
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  2. F Länger
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Tessema, M., Länger, F., Dingemann, J. et al. Aberrant methylation and impaired expression of the p15INK4b cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML). Leukemia 17, 910–918 (2003). https://doi.org/10.1038/sj.leu.2402891

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