Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia

Lynda B. Bennett, Kristen H. Taylor, Gerald L. Arthur, Farahnaz B. Rahmatpanah, Sam I. Hooshmand, Charles W. Caldwell

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations

Abstract

Certain WNT and WNT network target genes are expressed at higher or lower levels in chronic lymphocytic leukemia compared with normal B-cells. This includes upregulation of nuclear complex genes, as well as genes for cytoplasmic proteins and WNT ligands and their cognate receptors. In addition, epigenetic silencing of several negative regulators of the WNT pathway have been identified. The balance between epigenetic downregulation of negative effector genes and increased expression of positive effector genes demonstrate that the epigenetic downregulation of WNT antagonists is one mechanism, perhaps the main mechanism, that is permissive to active WNT signaling in chronic lymphocytic leukemia. Moreover, constitutive activation of the WNT network and target genes is likely to impact on additional interacting signaling pathways. Based on published studies, we propose a model of WNT signaling that involves mainly permissive expression, and sometimes overexpression, of positive effectors and downregulation of negative regulators in the network. In this model, DNA methylation, histone modifications and altered expression of microRNA molecules interact to allow continuous WNT signaling.

Original languageEnglish (US)
Pages (from-to)53-70
Number of pages18
JournalEpigenomics
Volume2
Issue number1
DOIs
StatePublished - Feb 2010

Keywords

  • DNA methylation
  • WNT pathway
  • chronic lymphocytic leukemia
  • epigenetics
  • histone modification
  • microRNAs

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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