Annals of Hematology

, Volume 84, Supplement 1, pp 39–46 | Cite as

Clinical implications of aberrant DNA methylation patterns in acute myelogenous leukemia

  • Oliver Galm
  • Stefan Wilop
  • Christian Lüders
  • Edgar Jost
  • Gerald Gehbauer
  • James G. Herman
  • Rainhardt Osieka
Original Article


Hypermethylation of CpG islands near gene promoter regions is associated with transcriptional inactivation and represents an important mechanism of gene silencing in carcinogenesis. Such epigenetic phenomena can act alongside DNA mutations and deletions to disrupt tumor-suppressor gene function. The methylation status of the promoter-associated CpG islands from 11 well-characterized cancer-related genes was analyzed by methylation-specific polymerase chain reaction in 60 adult patients with acute myelogenous leukemia (AML) at diagnosis. The frequency of aberrant methylation among the patient samples was 45.0% (27/60) for suppressor of cytokine signaling-1, 31.7% (19/60) for p15, 20.0% (12/60) for retinoic acid receptor β2, 13.3% (8/60) for p73 and E-cadherin, 5.0% (3/60) for O6-methylguanine DNA methyltransferase, 3.3% (2/60) for death-associated protein kinase 1 and hMLH1, 1.7% (1/60) for p16, and 0% (0/60) for the tissue inhibitor of matrix metalloproteinases-3 and Ras association domain family 1A. Aberrant DNA methylation was found in AML of all French–American–British subtypes and throughout all cytogenetic risk groups. There appeared to be a trend towards a higher methylation frequency in AML patients with an unfavorable karyotype, but this difference was not statistically significant. Our data indicate that hypermethylation of multiple genes involving fundamental cellular pathways is a common event in AML, which varies greatly in frequency among the genes examined. The accumulation of epigenetic events affecting genes which are involved in regulating cell cycle inhibition, cell adhesion, growth factor signaling, and apoptosis may contribute to the malignant AML phenotype. The growing knowledge of the role of epigenetics in the aberrant silencing of cancer-related genes provides a rationale and molecular basis for targeted therapeutic approaches with demethylating agents in AML.


DNA methylation Tumor-suppressor genes Acute myelogenous leukemia Epigenetics Methylation profile Demethylating agents 



We would like to thank Sandra Mellen and Ingeborg Wiegand for expert technical assistance and Albert Esser for help with the statistical analysis. We also thank Dr. Michael Lübbert for critical reading of the manuscript and helpful discussion. This work was supported by a grant from the Rheinisch-Westfälische Technische Hochschule Aachen (START program). JGH is a paid consultant to and receives research support from OncoMethylome Sciences. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Oliver Galm
    • 1
  • Stefan Wilop
    • 1
  • Christian Lüders
    • 1
  • Edgar Jost
    • 1
  • Gerald Gehbauer
    • 1
  • James G. Herman
    • 2
  • Rainhardt Osieka
    • 1
  1. 1.Medizinische Klinik IVUniversitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule AachenAachenGermany
  2. 2.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA

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