The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

Abstract

Background Therapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely variable,and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, thisstudy aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) genepolymorphic variants among adult ALL patients. We also investigated the association betweenGR messenger ribonucleic acid (mRNA) isoform expressions and the response tochemotherapy. Methods Fifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy controlsubjects were enrolled in this study. Genotyping was carried out using a polymerase chainreaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform expressionswere assayed by quantitative real-time PCR. Results ALL patients in this study had a median age of 34 years (range, 18-75). GRα expressionwas associated with complete remission (P=0.03), while GRγ mRNA expression was significantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019).However, there were no significant associations with GC resistance. The BclI polymorphicvariant of the GR gene was the most frequent in adult ALL patients and was not associatedwith the GC response. Both higher GRα expression and lower GRγ expression were associatedwith achievement of complete remission, while higher GRγ expression was associatedwith GC-resistance. Conclusion Our data suggest that the level of GR isoform expression may be useful in predicting GCresponse, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted.