Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures

Nucleic Acids Res. 2015 Mar 11;43(5):2590-602. doi: 10.1093/nar/gkv103. Epub 2015 Feb 17.


We investigated DNA methylomes of pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. Epigenetic alteration of B-ALLs occurred in two tracks: de novo methylation of small functional compartments and demethylation of large inter-compartmental backbones. The deviations were exaggerated in lamina-associated domains, with differences corresponding to methylation clusters and/or cytogenetic groups. Our data also suggested a pivotal role of polycomb and CTBP2 in de novo methylation, which may be traced back to bivalency status of embryonic stem cells. Driven by these potent epigenetic modulations, suppression of polycomb target genes was observed along with disruption of developmental fate and cell cycle and mismatch repair pathways and altered activities of key upstream regulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Child
  • Co-Repressor Proteins
  • CpG Islands / genetics
  • DNA Methylation*
  • Embryonic Stem Cells / metabolism*
  • Epigenomics / methods*
  • Gene Expression Profiling / methods*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Methylation
  • Neoplasm Proteins
  • Nerve Tissue Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Polycomb Repressive Complex 2 / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cells, B-Lymphoid / metabolism
  • Precursor Cells, B-Lymphoid / pathology
  • Signal Transduction / genetics
  • Transcription Factors


  • Co-Repressor Proteins
  • Histones
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • SUZ12 protein, human
  • Transcription Factors
  • Alcohol Oxidoreductases
  • CTBP2 protein, human
  • Polycomb Repressive Complex 2
  • Lysine

Associated data

  • GEO/GSE56602