Deakin University
Browse
ashley-distinctdnamethylation-2012.pdf (1.74 MB)

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

Download (1.74 MB)
journal contribution
posted on 2012-01-01, 00:00 authored by N Wong, David Ashley, Z Chatterton, M Parkinson-Bates, H Ng, M Halemba, A Kowalczyk, J Bedo, Q Wang, K Bell, E Algar, Jeffrey CraigJeffrey Craig, R Saffery
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.

History

Journal

Epigenetics

Volume

7

Issue

6

Pagination

535 - 541

Publisher

Landes Bioscience

Location

Georgetown, Tex.

ISSN

1559-2308

eISSN

1559-2294

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal