caa a22 4500 475773993 CHVBK 20180406123625.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s004180000165 doi (NATIONALLICENCE)springer-10.1007/s004180000165 Kofler R. Division of Molecular Pathophysiology, Institute for General and Experimental Pathology, University of Innsbruck Medical School and the Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria aut The molecular basis of glucocorticoid-induced apoptosis of lymphoblastic leukemia cells [Elektronische Daten] [R. Kofler] Abstract.: Glucocorticoids (GCs) induce programmed cell death with the morphologic characteristics of apoptosis in cells of the lymphoid lineage at certain stages of differentiation. Although the physiological significance of this phenomenon is not well understood, it has been exploited to a great extent in the therapy of malignant lymphoproliferative disorders. In spite of its clinical importance, the molecular mechanisms underlying GC-induced apoptosis and - clinically even more important - resistance to this phenomenon are not known. This review summarizes efforts from our and other laboratories addressing these issues in human lymphoblastic leukemia, with particular emphasis on the CCRF-CEM childhood T-cell leukemia model. These studies have shed some light on the downstream execution phase of GC-induced apoptosis but the critical upstream gene regulatory events have remained a mystery. Very recent DNA chip-based expression profile analyses in our laboratory along with data from the literature have, however, suggested that GC receptor auto-upregulation in sensitive target cells might be the critical event leading to persistent downregulation of central metabolic pathways which is incompatible with cell survival. The validity of this hypothesis and its possible clinical implications are currently being investigated in our laboratory. Springer-Verlag, 2000 Glucocorticoid-induced apoptosis Lymphatic leukemia Pathophysiology DNA chip analysis CCRF-CEM nationallicence https://doi.org/10.1007/s004180000165 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004180000165 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Kofler R. Division of Molecular Pathophysiology, Institute for General and Experimental Pathology, University of Innsbruck Medical School and the Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, Austria aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer