Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.

Bibliographic Details
Title: Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.
Authors: Magnus Borssén, Lars Palmqvist, Kristina Karrman, Jonas Abrahamsson, Mikael Behrendtz, Jesper Heldrup, Erik Forestier, Göran Roos, Sofie Degerman
Source: PLoS ONE, Vol 8, Iss 6, p e65373 (2013)
Publisher Information: Public Library of Science (PLoS), 2013.
Publication Year: 2013
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: BACKGROUND: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. DESIGN AND METHODS: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32). RESULTS: Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP- (low methylation). CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. CONCLUSIONS: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC3675104?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0065373
Access URL: https://doaj.org/article/4a9fc649c6ab4590b5c47543d9e4411b
Accession Number: edsdoj.4a9fc649c6ab4590b5c47543d9e4411b
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0065373
Published in:PLoS ONE
Language:English