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Promoter DNA Methylation Pattern Identifies Prognostic Subgroups in Childhood T-Cell Acute Lymphoblastic Leukemia
Umeå University, Sweden.
Sahlgrenska University Hospital, University of Gothenburg, Sweden.
Skåne University Hospital, Lund University, Sweden.
Sahlgrenska University Hospital, Gothenburg, Sweden.
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2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 6Article in journal (Refereed) Published
Abstract [en]


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).


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.


We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

Place, publisher, year, edition, pages
Public Library of Science , 2013. Vol. 8, no 6
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-95967DOI: 10.1371/journal.pone.0065373ISI: 000321099000061PubMedID: 23762353OAI: diva2:649038

Funding Agencies|Swedish Cancer Society||Swedish Research Council||Swedish Childhood Cancer Foundation||Medical Faculty, Umea University||Lions Cancer Research Foundation, Umea||European Community|200950|

Available from: 2013-09-17 Created: 2013-08-12 Last updated: 2014-06-09Bibliographically approved

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