High level of glutathione-S-transferase pi expression in mantle cell lymphomas.
OBJECTIVE
Prognosis of mantle cell lymphoma (MCL) remains poor. Patients who achieve a response to first line therapy usually relapse, and the probability of cure remains low. Glutathione-S-transferase pi (GST-pi) overexpression has been associated with alkylating agents and anthracycline resistance. GST-pi gene is located in 11q13 and is coamplified along with CCND1 gene in some human solid tumors.


METHODS
We performed immunohistochemical analysis of GST-pi expression in 24 consecutive MCLs, 12 follicular lymphomas (FLs), and 69 diffuse large B-cell lymphomas (DLBCLs). Cases were classified in three groups: high GST-pi expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST-pi and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis.


RESULTS
All MCLs exhibit high GST-pi protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST-pi and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST-pi and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST-pi expression is high in MCL compared with FL and DLBCL.


CONCLUSIONS
Overexpression of CCND1 in MCL is associated with a transcriptional up-regulation of the GST-pi gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.
Bennaceur-Griscelli
Annelise
A
Département de Biologie Clinique, Laboratoire d'Hématologie, Institut Gustave Roussy, Villejuif, France.
Bosq
Jacques
J
Koscielny
Serge
S
Lefrère
François
F
Turhan
Ali
A
Brousse
Nicole
N
Hermine
Olivier
O
Ribrag
Vincent
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D007527:Isoenzymes; D012333:RNA, Messenger; D019938:Cyclin D1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase