Role of γ-glutamyl cysteine synthetase (γ-GCS) gene expression as marker of drug sensitivity in acute myeloid leukemias

BackgroundElevated levels of glutathione (GSH) have been reported to play an important role in mediating chemoresistance in tumor cells. The regulation of γ-glutamylcysteine synthetase (γ-GCS) is one of the major determinants of GSH homeostasis. The aim of our study was to investigate γ-GCS gene expression in patients affected by acute myeloid leukemia (AML).MethodsA total of 64 AML samples, including 23 acute promyelocytic leukemia (APL or M3) cases, were included in the study. γ-GCS mRNA levels were determined by real-time quantitative RT-PCR. All patients were evaluated at diagnosis, whereas post-treatment γ-GCS mRNA levels were assessed at the end of the consolidation therapy in 16 cases.ResultsOur data showed that variable degrees of γ-GCS expression were detectable in AML, likely reflecting disease heterogeneity; in particular, APL cases, compared to the other AML subsets, showed both significantly lower basal levels of γ-GCS mRNA at presentation and significantly increased mRNA levels after treatment.ConclusionsDecreased levels of γ-GCS leading to reduced GSH may at least in part explain the higher sensitivity of APL to chemotherapy.