Interleukin-3-mediated regulation of beta-catenin in myeloid transformation and acute myeloid leukemia
Details
Publication Year 2014-07, Volume 96, Issue #1, Page 83-91
Journal Title
J Leukoc Biol
Publication Type
Journal Article
Abstract
Aberrant activation of beta-catenin is a common event in AML and is an independent predictor of poor prognosis. Although increased beta-catenin signaling in AML has been associated with oncogenic translocation products and activating mutations in the FLT3R, the mechanisms that activate beta-catenin in AML more broadly are still unclear. Here, we describe a novel link between IL-3 signaling and the regulation of beta-catenin in myeloid transformation and AML. In a murine model of HoxB8 and IL-3 cooperation, we show that beta-catenin protein levels are modulated by IL-3 and that Cre-induced deletion of beta-catenin abolishes IL-3-dependent growth and colony formation. In IL-3-dependent leukemic TF-1.8 cells, we observed increased beta-catenin protein levels and nuclear localization in response to IL-3, and this correlated with transcriptional induction of beta-catenin target genes. Furthermore, IL-3 promoted beta-catenin accumulation in a subset of AML patient samples, and gene-expression profiling of these cells revealed induction of WNT/beta-catenin and TCF4 gene signatures in an IL-3-dependent manner. This study is the first to link beta-catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of beta-catenin activity in some patients with AML.
Publisher
Society for Leukocyte Biology
WEHI Research Division(s)
Cell Signalling And Cell Death
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2014-09-15 12:08:27
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙