Epigenetic deregulation in pediatric acute lymphoblastic leukemia

Zac Chatterton, Leah Morenos, Francoise Mechinaud, David M. Ashley, Jeffrey M. Craig, Alexandra Sexton-Oates, Minhee S. Halemba, Mandy Parkinson-Bates, Jane Ng, Debra Morrison, William L. Carroll, Richard Saffery, Nicholas C. Wong

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the EPO-receptor, while Hyperdiploid patients (>50 chr) displayed upregulation of B-cell lymphoma (BCL) members and repression of PTPRG and FHIT. In combination, these data indicate genetically distinct B-cell ALL subtypes contain cooperative epimutations and genome-wide epigenetic deregulation is common across all B-cell ALL subtypes.

Original languageEnglish
Pages (from-to)459-467
Number of pages9
Issue number3
StatePublished - 6 Jan 2014
Externally publishedYes


  • ALL
  • Acute lymphoblastic leukemia
  • B-cell
  • DNA methylation
  • Epigenetics
  • Hematology
  • Leukemia


Dive into the research topics of 'Epigenetic deregulation in pediatric acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this