KIT-D816V–independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib

• Published in: Blood Vol. 118; no. 7; pp. 1885 - 1898
• Main Authors: Gleixner, Karoline V., Mayerhofer, Matthias, Cerny-Reiterer, Sabine, Hörmann, Gregor, Rix, Uwe, Bennett, Keiryn L., Hadzijusufovic, Emir, Meyer, Renata A., Pickl, Winfried F., Gotlib, Jason, Horny, Hans-Peter, Reiter, Andreas, Mitterbauer-Hohendanner, Gerlinde, Superti-Furga, Giulio, Valent, Peter
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 18.08.2011; Americain Society of Hematology
• Subjects: Agammaglobulinaemia Tyrosine Kinase; Aniline Compounds - pharmacology; Biological and medical sciences; Cell Line, Tumor; Dasatinib; Drug Synergism; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Mast Cells - metabolism; Mast Cells - pathology; Mastocytosis, Systemic - drug therapy; Mastocytosis, Systemic - genetics; Mastocytosis, Systemic - metabolism; Medical sciences; Mutation; Nitriles - pharmacology; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Pyrimidines - pharmacology; Quinolines - pharmacology; Signal Transduction - drug effects; src-Family Kinases - genetics; src-Family Kinases - metabolism; Staurosporine - analogs & derivatives; Staurosporine - pharmacology; Thiazoles - pharmacology; Tumor Cells, Cultured; Antineoplastic agent; Dasatinib; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Lyn protein tyrosine kinase; Malignant hemopathy; Malignant tumor; Bosutinib; Systemic mastocytosis; Signal transduction; Bruton tyrosine kinase; Multikinase inhibitor; Protein-tyrosine kinase; Protooncogene; Cancer

Systemic mastocytosis (SM) either presents as a malignant neoplasm with short survival or as an indolent disease with normal life expectancy. In both instances, neoplastic mast cells (MCs) harbor D816V-mutated KIT, suggesting that additional oncogenic mechanisms are involved in malignant transformat...