Targeting the oncogenic tyrosine kinase NPM-ALK in lymphoma: the role of murine models in defining pathogenesis and treatment options.
Oncogenic tyrosine kinases play a ever growing role in the pathogenesis of human malignancies. In human non-Hodgkin lymphomas, the NPM-ALK oncogene arising from the t(2;5) chromosomal translocation represents the most important oncogenic tyrosine kinase identified so far. The ALK-kinase is constitutively activated by NPM-induced dimerization and signals through a multitude of growth promoting and antiapoptotic pathways. Murine models have made a significant impact on the elucidation of the molecular pathogenesis and new treatment options of malignant diseases. Here, the latest developments in the analysis of NPM-ALK induced lymphomagenesis by murine models is reviewed.
Miething
Cornelius
C
Department of Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Trogerstr. 32, D-81675 Munich, Germany.
Peschel
Christian
C
Duyster
Justus
J
D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology* / Q000628:therapy*; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004791:Enzyme Inhibitors; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases