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Aberrant methylation and impaired expression of the p15 INK4b cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML)

Aberrant methylation and impaired expression of the p15 INK4b cell cycle regulatory gene in... The important cell cycle regulatory gene p15 INK4b 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 p15 INK4b 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Leukemia Springer Journals

Aberrant methylation and impaired expression of the p15 INK4b cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML)

Tessema, M; Länger, F; Dingemann, J; Ganser, A; Kreipe, H; Lehmann, U
Leukemia , Volume 17 (5) – May 15, 2003
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References (31)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Nature Publishing Group
Subject
Medicine & Public Health; Medicine/Public Health, general; Internal Medicine; Intensive / Critical Care Medicine; Cancer Research; Oncology; Hematology
ISSN
0887-6924
eISSN
1476-5551
DOI
10.1038/sj.leu.2402891
Publisher site
See Article on Publisher Site

Abstract

The important cell cycle regulatory gene p15 INK4b 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 p15 INK4b 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.

Journal

Leukemia – Springer Journals

Published: May 15, 2003

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