%0 Journal Article %A FLORIAN PERNER %A TINA M. SCHNÖDER %A THOMAS FISCHER %A FLORIAN H. HEIDEL %T Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in FLT3-ITD-positive AML %D 2016 %J Anticancer Research %P 6249-6258 %V 36 %N 12 %X Background/Aim: The presence of FLT3-Internal tandem duplications (ITDs) in human acute myeloid leukemia (AML) is associated with a dismal prognosis. Altered cell-cycle activity has been reported in FLT3-ITD-positive AML; however, the mechanisms by which this oncogene influences cell-cycle activity remained so far elusive. Materials and Methods: A phospho-kinomic screen was used to identify downstream effectors of FLT3-ITD. Validation and functional characterization was performed by western blotting, cell-cycle analysis and apoptosis assays. Results: We identified aberrant phosphorylation of CDC25C-T48 in FLT3-ITD mutated cells. Forced expression of CDC25C affected cell-cycle progression but did not affect sensitivity to cellular stress. Conclusion: Depending on the oncogenic background, CDC25C may reveal protective or oncogenic functions. Our results identify CDC25C as a downstream target of the mutated tyrosine kinase FLT3-ITD affecting cell-cycle regulation in a model of AML. %U https://ar.iiarjournals.org/content/anticanres/36/12/6249.full.pdf