title: Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia.
abstract: Glucocorticoid (GC) resistance is a phenomenon of major significance in a number of clinical situations, including the therapy of lymphoid malignancies. Resistance may concern all, or just selected, GC effects, it may be absolute or just reflect a state of reduced sensitivity and, clinically relevant, be reversible or irreversible. Numerous molecular mechanisms can be envisaged acting either 'upstream' in the GC-triggered signaling pathway, i.e. at the level of the GC receptor (GR), or 'downstream' at the level of the GC-regulated genes responsible for individual GC effects. In lymphoid malignancies, GCs have anti-leukemic effects through the induction of apoptosis and/or cell cycle arrest. In this condition evidence for only a small number of mechanisms for GC resistance has been provided, mostly at the level of the GR. Herein, we review reports and hypotheses regarding 'upstream' and 'downstream' mechanisms for GC resistance in lymphoblastic leukemia and present an in vitro GC resistance model that might allow identification of resistance mechanisms.
authors.affiliation: Tyrolean Cancer Research Institute at the University of Innsbruck, Austria. reinhard.kofler@uibk.ac.at
authors.forename: R
authors.initials: R
authors.lastname: Kofler
authors.forename: S
authors.initials: S
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Kofler
authors.forename: M J
authors.initials: MJ
authors.lastname: Ausserlechner
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004351:Drug Resistance; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid