title: Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Borssén
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Kristina
authors.initials: K
authors.lastname: Karrman
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Behrendtz
authors.forename: Jesper
authors.initials: J
authors.lastname: Heldrup
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Sofie
authors.initials: S
authors.lastname: Degerman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis
chemical_list: D009363:Neoplasm Proteins