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 article

15 Citations (Scopus)

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 1 2010
Externally publishedYes

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Epigenomics
Down-Regulation
Gene Regulatory Networks
Histone Code
DNA Methylation
MicroRNAs
Genes
B-Lymphocytes
Up-Regulation
Ligands
Gene Expression
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Bennett, L. B., Taylor, K. H., Arthur, G. L., Rahmatpanah, F. B., Hooshmand, S. I., & Caldwell, C. W. (2010). Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia. Epigenomics, 2(1), 53-70. https://doi.org/10.2217/epi.09.43

Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia. / Bennett, Lynda B.; Taylor, Kristen H.; Arthur, Gerald L.; Rahmatpanah, Farahnaz B.; Hooshmand, Sam I.; Caldwell, Charles W.

In: Epigenomics, Vol. 2, No. 1, 01.02.2010, p. 53-70.

Research output: Contribution to journalReview article

Bennett, LB, Taylor, KH, Arthur, GL, Rahmatpanah, FB, Hooshmand, SI & Caldwell, CW 2010, 'Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia', Epigenomics, vol. 2, no. 1, pp. 53-70. https://doi.org/10.2217/epi.09.43
Bennett LB, Taylor KH, Arthur GL, Rahmatpanah FB, Hooshmand SI, Caldwell CW. Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia. Epigenomics. 2010 Feb 1;2(1):53-70. https://doi.org/10.2217/epi.09.43
Bennett, Lynda B. ; Taylor, Kristen H. ; Arthur, Gerald L. ; Rahmatpanah, Farahnaz B. ; Hooshmand, Sam I. ; Caldwell, Charles W. / Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia. In: Epigenomics. 2010 ; Vol. 2, No. 1. pp. 53-70.
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