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

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.

Keywords::

• CpG island
• DNA methylation
• leukemia
• prognostic marker
• remission

Acknowledgement

The authors thank A Moorman, Newcastle University, for critical reading of the manuscript.

Financial & competing interests disclosure

This work was supported by a PhD scholarship from the NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease awarded to GS and SDvO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by a PhD scholarship from the NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease awarded to GS and SDvO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.