Differential mRNA expression of glucocorticoid receptor α and β is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children

Background. Sensitivity of leukemic blasts to glucocorticoid is one of the important prognostic factors for pediatric acute lymphoblastic leukemia (ALL). Alternative splicing of the glucocorticoid receptor (GR) gene results in several isoforms. We examined an association of the expression pattern of GR isoforms in leukemic blasts with their sensitivity to glucocorticoid in childhood ALL. Procedures. The relative mRNA expression of GRα, GRβ, GRγ, and GR-P was determined in leukemic blasts of 23 childhood ALL at initial presentation and of 14 ALL cell lines by quantitative RT-PCR. Glucocorticoid-sensitivity of leukemic blasts was determined by counting apoptotic cells with flow cytometry after 6-hr incubation with prednisolone (PSL). Results. The relative expression of GRα mRNA was significantly higher in blasts of B-precursor ALL than those of others (13.6 vs. 2.24, P = 0.015), while those of GRα, GRβ, and GRγ showed no difference. GRβ/GRα ratios were significantly lower in B-precursor ALL than others (0.80 vs. 4.64, P = 0.035). The proportions of apoptotic cells after PSL exposure were inversely correlated with the GRβ/GRα ratios in ALL cell lines (r = -0.612, P=0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRβ/GRα ratios compared with those of high ratios (cell lines: 4.93% vs. 1.90%, P = 0.013, primary leukemia: 11.7% vs. 3.6%, P = 0.037). Conclusions. The amounts of GR isoform mRNA in leukemic blasts were closely correlated with sensitivity to glucocorticoid exposure. The mRNA expression pattern of GR isoforms at initial presentation may provide valuable information for prognosis in children with newly diagnosed ALL.