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Epigenetics. 2014 Mar;9(3):459-67. doi: 10.4161/epi.27585. Epub 2014 Jan 6.

Epigenetic deregulation in pediatric acute lymphoblastic leukemia.

Author information

1
Murdoch Childrens Research Institute; The University of Melbourne Department of Paediatrics at the Royal Children's Hospital; Victoria, VIC Australia.
2
Childrens Cancer Centre; Royal Children's Hospital; Victoria, VIC Australia.
3
Andrew Love Cancer Centre; Deakin University; Victoria, VIC Australia.
4
New York University Cancer Institute; New York, NY USA.

Abstract

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.

KEYWORDS:

ALL; B-cell; DNA methylation; acute lymphoblastic leukemia; epigenetics; hematology; leukemia

PMID:
24394348
PMCID:
PMC4053464
DOI:
10.4161/epi.27585
[Indexed for MEDLINE]
Free PMC Article
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