Role of gamma-glutamyl cysteine synthetase (gamma-GCS) gene expression as marker of drug sensitivity in acute myeloid leukemias.
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.
Carnicer
Maria José
MJ
Department of Biopathology and Department of Laboratory Medicine-PTV, University of Rome "Tor Vergata", Italy.
Bernardini
Sergio
S
Bellincampi
Lorenza
L
Noguera
Nelida Inés
NI
Nuccetelli
Marzia
M
Ammatuna
Emanuele
E
Breccia
Massimo
M
Lo-Coco
Francesco
F
Federici
Giorgio
G
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
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase