Gene-specific and global methylation patterns predict outcome in patients with acute myeloid leukemia

Leukemia. 2010 May;24(5):932-41. doi: 10.1038/leu.2010.41. Epub 2010 Mar 18.


This study was designed to analyze the effect of global and gene-specific DNA methylation patterns on the outcome of patients with acute myeloid leukemia (AML). Methylation of CDKN2B (p15), E-cadherin (CDH) and hypermethylated in cancer 1 (HIC1) promoters and global DNA methylation by luminometric methylation assay (LUMA) was analyzed in 107 AML patients and cytogenetic and molecular mutational analysis was performed. In addition, genome-wide promoter-associated methylation was assessed using the Illumina HumanMethylation27 array in a proportion of the patients. Promoter methylation was discovered in 66, 66 and 51% of the patients for p15, CDH and HIC1, respectively. In multivariate analysis, low global DNA methylation was associated with higher complete remission rate (hazard ratio (HR) 5.9, P=0.005) and p15 methylation was associated with better overall (HR 0.4, P=0.001) and disease-free survival (HR 0.4, P=0.016). CDH and HIC1 methylation were not associated with clinical outcome. Mutational status and karyotype were not significantly associated with gene-specific methylation or global methylation. Increased genome-wide promoter-associated methylation was associated with better overall and disease-free survival as well as with LUMA hypomethylation. We conclude that global and gene-specific methylation patterns are independently associated with the clinical outcome in AML patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Cadherins / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • DNA Methylation*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / classification
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Remission Induction
  • Survival Rate
  • Treatment Outcome
  • Young Adult


  • Biomarkers, Tumor
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p15