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

M. J. Carnicer, Sergio Bernardini, Lorenza Bellincampi, N. I. Noguera, Marzia Nuccetelli, Emanuele Ammatuna, Massimo Breccia, Francesco Lo-Coco, Giorgio Federici

Research output: Contribution to journalArticle

Abstract

Background: Elevated 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). Methods: A 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. Results: Our 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. Conclusions: Decreased levels of γ-GCS leading to reduced GSH may at least in part explain the higher sensitivity of APL to chemotherapy.

Original languageEnglish
Pages (from-to)342-345
Number of pages4
JournalClinica Chimica Acta
Volume365
Issue number1-2
DOIs
Publication statusPublished - Mar 2006

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Keywords

  • γ-glutamyl cysteine synthetase
  • Acute myeloid leukemia
  • Acute promyelocytic leukemia
  • Glutathione transferase P1-1

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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