Epigenetic deregulation in pediatric acute lymphoblastic leukemia.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chatterton, Z; Morenos, L; Mechinaud, F; Ashley, DM; Craig, JM; Sexton-Oates, A; Halemba, MS; Parkinson-Bates, M; Ng, J; Morrison, D; Carroll, WL; Saffery, R; Wong, NC

Published Date

  • March 2014

Published In

Volume / Issue

  • 9 / 3

Start / End Page

  • 459 - 467

PubMed ID

  • 24394348

Pubmed Central ID

  • 24394348

Electronic International Standard Serial Number (EISSN)

  • 1559-2308

Digital Object Identifier (DOI)

  • 10.4161/epi.27585

Language

  • eng

Conference Location

  • United States