title: Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies.
abstract: Myeloid malignancies frequently harbor specific mutations in protein tyrosine kinases leading to oncogenic cell signaling. The most extensively investigated example is chronic myeloid leukemia, where the pathogenic tyrosine kinase fusion protein Bcr-Abl is a successful target for disease control by the specific inhibitor imatinib mesylate. In acute myeloid leukemia the receptor tyrosine kinase Flt3 is frequently mutated and inhibitors to impair the oncogenic signaling are in development. In this review we exemplify oncogenic signaling and how signal pathways can be unraveled with help from proteomics-based technologies. The distinction between cell extract and single cell approaches aiming at rigorous standardization and reliable quantitative aspects for future proteomics-based diagnostics is discussed.
authors.affiliation: Proteomic Unit in Bergen, University of Bergen, Bergen, Norway.
authors.forename: Eystein
authors.initials: E
authors.lastname: Oveland
authors.forename: Kari E
authors.initials: KE
authors.lastname: Fladmark
authors.forename: Line
authors.initials: L
authors.lastname: Wergeland
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Randi
authors.initials: R
authors.lastname: Hovland
mesh_terms: D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D010766:Phosphorylation; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases