Aberrations in DNA methylation are detectable during remission of acute lymphoblastic leukemia and predict patient outcome

Author:

van Otterdijk Sanne D1,Norden Jean2,Dickinson Anne M2,Pearce Mark S3,Relton Caroline L45,Mathers John C6,Strathdee Gordon1

Affiliation:

1. Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne, UK

2. Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK

3. Institute of Health & Society, Newcastle University, Newcastle Upon Tyne, UK

4. Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK

5. MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, UK

6. Human Nutrition Research Centre, Institute for Ageing & Health, Campus for Ageing & Vitality, Newcastle University, Newcastle Upon Tyne, UK

Abstract

Aim: Aberrant DNA methylation patterns are a hallmark of cancer, although the extent to which they underlie cancer development is unknown. In this study, we aimed to determine whether acute lymphoblastic leukemia (ALL) patients in clinical remission retained abnormal DNA methylation patters and whether these were associated with patient outcome. Materials & methods: We investigated CpG island methylation of genes known to exhibit hypermethylation in leukemia using quantitative pyrosequencing analysis. Results: Although methylation levels were reduced in remission samples, they remained significantly higher than those seen in healthy controls. This retained methylation was not related to low levels of residual leukemia cells still present at remission. Methylation levels were also stable (or increased) during continuous remission and significantly correlated with long-term survival in adult ALL patients. Conclusion: This study determined that abnormalities in DNA methylation are retained during ALL remission and may represent a novel prognostic marker for adult ALL patients.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

Reference35 articles.

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