A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Nicholas C Wong, David Ashley, Zac Chatterton, Mandy Parkinson-Bates, Hong Kiat Ng, Minhee S. Halemba, Adam Kowalczyk, Justin Bedo, Qiao Jerry Wang, Katrina M Bell, Elizabeth Algar, Jeffrey M. Craig, Richard Saffery

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30 Citations (Scopus)

Abstract

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34 + cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.
Original languageEnglish
Pages (from-to)535-541
Number of pages7
JournalEpigenetics
Volume7
Issue number6
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

Keywords

  • Childhood acute lymphoblastic leukemia
  • DNA methylation
  • Pre B cell acute lymphoblastic leukemia

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