Molecular mechanisms of apoptosis induced by dexamethasone in chronic lymphocytic leukemia

摘要: Glucocorticoids are frequently included in the chemotherapy regimens administered to patients with CLL because they potent immunosuppressant agents and able induce apoptosis cells. Although used from a long time, molecular mechanisms by which glucocorticoids cell death cells largely unknown. Interestingly, prognostic groups defined mutational load of IGHV genes expression ZAP70 seem have different responses glucocorticoids. The hypothesis this thesis is that there or proteins determine response among specific CLL. Sensitivity dexamethasone was analyzed ex vivo 50 compared according status and/or expression. further gene profiling (GEP) selected cases. Expression interest validated quantitative reverse transcriptase PCR. Response higher cases unmutated IGHV/high levels induction pro-apoptotic BIM gen correlate degree death. induced observed translate into profiles These differences mainly quantitative; high show induction/repression than low Specific analysis performed large series disclosed baseline mRNA protein FKBP5, co-chaperone glucocorticoid receptor, extent treatment dexamethasone. Baseline FKBP5 samples GILZ differentially CLL, being Induction correlates apoptosis. Unmutated exhibit better treatment, accompanied differential involved glucocorticoid-receptor pathway an increased related