Glucocorticoid receptor alpha, beta and gamma expression vs in vitro glucocorticod resistance in childhood leukemia

Abstract
Alternative splicing of the primary glucocorticoid receptor (GR) transcript, resulting in glucocorticoid receptor alpha GR, glucocorticoid receptor beta GR and glucocorticoid receptor gamma GR, may influence glucocorticoid (GC) resistance in childhood leukemia. To test this hypothesis, we determined GR/ protein and GR// mRNA expression levels in 43 initial acute lymphoblastic leukemia (iALL), 10 initial myeloid leukemia (iAML), 11 relapsed ALL (rALL) samples and one rAML sample. The results were correlated with in vitro GC resistance. GR mRNA correlated with protein expression (=0.39–0.56, PP mRNA was median 137-fold lower than GR mRNA and correlated with GR mRNA expression (=0.71, P could not be detected at the protein level. GR accounted for a median of 2.8% (range 0.95–7.4%) of all GR transcripts. GR (protein and mRNA) and GR (mRNA) expressions or GR/GR ratios did not correlate with in vitro GC resistance in iALL, but GR (mRNA) did (=0.52, P=0.007). These results suggest that GR is not involved in GC resistance in childhood leukemia. The association between GR expression and in vitro GC resistance in iALL and the decreased protein/mRNA ratio in rALL, a subgroup resistant to GCs, warrants further exploration.