Epigenetic deregulation in pediatric acute lymphoblastic leukemia

Zac Chatterton, Leah Morenos, Francoise Mechinaud, David M. Ashley, Jeffrey Mark 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 journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)459-467
Number of pages9
JournalEpigenetics
Volume9
Issue number3
DOIs
Publication statusPublished - 6 Jan 2014
Externally publishedYes

Keywords

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

Cite this

Chatterton, Z., Morenos, L., Mechinaud, F., Ashley, D. M., Craig, J. M., Sexton-Oates, A., ... Wong, N. C. (2014). Epigenetic deregulation in pediatric acute lymphoblastic leukemia. Epigenetics, 9(3), 459-467. https://doi.org/10.4161/epi.27585
Chatterton, Zac ; Morenos, Leah ; Mechinaud, Francoise ; Ashley, David M. ; Craig, Jeffrey Mark ; Sexton-Oates, Alexandra ; Halemba, Minhee S. ; Parkinson-Bates, Mandy ; Ng, Jane ; Morrison, Debra ; Carroll, William L. ; Saffery, Richard ; Wong, Nicholas C. / Epigenetic deregulation in pediatric acute lymphoblastic leukemia. In: Epigenetics. 2014 ; Vol. 9, No. 3. pp. 459-467.
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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 2014, 'Epigenetic deregulation in pediatric acute lymphoblastic leukemia' Epigenetics, vol. 9, no. 3, pp. 459-467. https://doi.org/10.4161/epi.27585

Epigenetic deregulation in pediatric acute lymphoblastic leukemia. / Chatterton, Zac; Morenos, Leah; Mechinaud, Francoise; Ashley, David M.; Craig, Jeffrey Mark; Sexton-Oates, Alexandra; Halemba, Minhee S.; Parkinson-Bates, Mandy; Ng, Jane; Morrison, Debra; Carroll, William L.; Saffery, Richard; Wong, Nicholas C.

In: Epigenetics, Vol. 9, No. 3, 06.01.2014, p. 459-467.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Morenos, Leah

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AU - Craig, Jeffrey Mark

AU - Sexton-Oates, Alexandra

AU - Halemba, Minhee S.

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AU - Wong, Nicholas C.

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Chatterton Z, Morenos L, Mechinaud F, Ashley DM, Craig JM, Sexton-Oates A et al. Epigenetic deregulation in pediatric acute lymphoblastic leukemia. Epigenetics. 2014 Jan 6;9(3):459-467. https://doi.org/10.4161/epi.27585