RT Journal Article
SR Electronic
T1 Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in <em>FLT3</em>-ITD-positive AML
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6249
OP 6258
VO 36
IS 12
A1 FLORIAN PERNER
A1 TINA M. SCHNÖDER
A1 THOMAS FISCHER
A1 FLORIAN H. HEIDEL
YR 2016
UL http://ar.iiarjournals.org/content/36/12/6249.abstract
AB 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.