Interleukin-3-mediated regulation of beta-catenin in myeloid transformation and acute myeloid leukemia
Teresa Sadras, Michelle Perugini, Chung H Kok, Diana G Iarossi, Susan L Heatley, Gabriela Brumatti, Michael S Samuel, Luen B To, Ian D Lewis, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw, Richard J D'Andrea
Journal of Leukocyte Biology | FEDERATION AMER SOC EXP BIOL | Published : 2014
Aberrant activation of β-catenin is a common event in AML and is an independent predictor of poor prognosis. Although increased β-catenin signaling in AML has been associated with oncogenic translocation products and activating mutations in the FLT3R, the mechanisms that activate β-catenin in AML more broadly are still unclear. Here, we describe a novel link between IL-3 signaling and the regulation of β-catenin in myeloid transformation and AML. In a murine model of HoxB8 and IL-3 cooperation, we show that β-catenin protein levels are modulated by IL-3 and that Cre-induced deletion of β-catenin abolishes IL-3-dependent growth and colony formation. In IL-3-dependent leukemic TF-1.8 cells, we..View full abstract
Awarded by National Health and Medical Research Council
The authors acknowledge funding obtained from the National Health and Medical Research Council (Project grant ID #626947) and financial contributions from an Australian postgraduate award and a Robinson Institute Postgraduate Scholarship in support of T. S. We also acknowledge the financial contributions provided by the Fred Shahin Early-Career Fellowship in support of M. P. and the Peter Nelson Leukemia Research Fellowship Fund in support of H.S.R.