title: Role of gamma-glutamyl cysteine synthetase (gamma-GCS) gene expression as marker of drug sensitivity in acute myeloid leukemias.
abstract: BACKGROUND
  Elevated levels of glutathione (GSH) have been reported to play an important role in mediating chemoresistance in tumor cells. The regulation of gamma-glutamylcysteine synthetase (gamma-GCS) is one of the major determinants of GSH homeostasis. The aim of our study was to investigate gamma-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. gamma-GCS mRNA levels were determined by real-time quantitative RT-PCR. All patients were evaluated at diagnosis, whereas post-treatment gamma-GCS mRNA levels were assessed at the end of the consolidation therapy in 16 cases.
  
  
  RESULTS
  Our data showed that variable degrees of gamma-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 gamma-GCS mRNA at presentation and significantly increased mRNA levels after treatment.
  
  
  CONCLUSIONS
  Decreased levels of gamma-GCS leading to reduced GSH may at least in part explain the higher sensitivity of APL to chemotherapy.
authors.affiliation: Department of Biopathology and Department of Laboratory Medicine-PTV, University of Rome "Tor Vergata", Italy.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Carnicer
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellincampi
authors.forename: Nelida Inés
authors.initials: NI
authors.lastname: Noguera
authors.forename: Marzia
authors.initials: M
authors.lastname: Nuccetelli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Ammatuna
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase