Changes of glucocorticoid receptor isoforms expression in acute lymphoblastic leukemia correlate with glucocorticoid resistance

Alternative splicing of the glucocorticoid receptor (GR) gene results in several GR isoforms, we examined their expression (GRα, GRβ, GRγ and GR-P) by real-time RT-PCR in glucocorticoid (GC) sensitive (CEM-C7), GC resistant (CEM-C1) cells and adult acute lymphoblastic leukemia (ALL) patients, to determine the association of GR isoform expression profiles and GC resistance in adult ALL patients. With GC treatment, GR levels in C1 cells showed no obvious changes. In C7 cells, the mRNA levels of GRα, GRβ and GRγ first increased and then decreased, whereas GR-P mRNA had a continued rising trend. C7 cells had a higher GRα/GRγ, lower GRα/GR-P and GRγ/GR-P ratios than C1 cells (P < 0.01). In adult ALL patients, GRγ mRNA varied in different ALL stages (complete remission CR 15.82 vs. relapsed 8.21 vs. initial 1.93 P < 0.05). It also did in the ratios between GR isoforms that GRα/GRγ and GRα/GR-P in initial patients were higher than relapsed and CR (P < 0.05), while GRγ/GR-P in CR was higher than initial and relapsed patients (P < 0.05). GR-P mRNA in T-ALL patients was much higher than that in B-ALL patients (P < 0.05). Peripheral blood hemoglobin (HB) was positively correlated with GRα mRNA and GR-P mRNA (P < 0.05), while white blood cells (WBC) negatively correlated with GRγ mRNA (P < 0.05). The present study demonstrates that GR autoinduction is more important to GC sensitivity than its basal level expression. GC sensitivity is also significantly correlated with GRα mRNA and mildly associated with GRβ mRNA expression. Both GRγ mRNA and the ratios between GR isoforms (GRα/GRγ, GRα/GR-P and GRγ/GR-P) are correlated with ALL stages. The changes of mRNA expression levels of GRα, GR-P and GRγ may provide valuable information for GC resistance. Peripheral blood HB and WBC affect GR isoform expression.