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

Deneberg S, Grövdal M, Karimi M, Jansson M, Nahi H, Corbacioglu A, Gaidzik V, Döhner K, Paul C, Ekström TJ, Hellström-Lindberg E, Lehmann S

Leukemia 24 (5) 932-941 [2010-05-00; online 2010-03-20]

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.

Bioinformatics and Expression Analysis (BEA)

PubMed 20237504

DOI 10.1038/leu.2010.41

Crossref 10.1038/leu.2010.41

pii: leu201041