Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies.
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.
Oveland
Eystein
E
Proteomic Unit in Bergen, University of Bergen, Bergen, Norway.
Fladmark
Kari E
KE
Wergeland
Line
L
Gjertsen
Bjørn Tore
BT
Hovland
Randi
R
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
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases