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Updated: Aug 17, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in FLT3-ITD-positive AML
Florian Perner1,2,3, Tina M Schnöder2,3, Thomas Fischer1,4
1Department of Hematology and Oncology, Center of Internal Medicine, Otto-von-Guericke University Medical Center, Magdeburg, Germany.
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.
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