title: Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in FLT3-ITD-positive AML.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hematology and Oncology, Center of Internal Medicine, Otto-von-Guericke University Medical Center, Magdeburg, Germany.|Internal medicine II, Hematology and Oncology, Friedrich-Schiller-University Medical Center, Jena, Germany.|Leibniz-Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Perner
authors.affiliation: Internal medicine II, Hematology and Oncology, Friedrich-Schiller-University Medical Center, Jena, Germany.|Leibniz-Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Schnöder
authors.affiliation: Department of Hematology and Oncology, Center of Internal Medicine, Otto-von-Guericke University Medical Center, Magdeburg, Germany.|Collaborative Research Cluster 854, Medical Faculty, Otto-von-Guericke University Medical Center, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Internal medicine II, Hematology and Oncology, Friedrich-Schiller-University Medical Center, Jena, Germany florian.h.heidel@gmail.com.|Leibniz-Institute on Aging, Fritz-Lipmann-Institute, Jena, Germany.|Collaborative Research Cluster 854, Medical Faculty, Otto-von-Guericke University Medical Center, Magdeburg, Germany.
authors.forename: Florian H
authors.initials: FH
authors.lastname: Heidel
mesh_terms: D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D010766:Phosphorylation; D020687:cdc25 Phosphatases / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases
keywords: AML; CDC25C; FLT3-ITD; Ser216; Thr48; cell cycle