Glutathione-S-transferases pi, alpha, mu and mdr1 mRNA expression in normal lymphocytes and chronic lymphocytic leukemia.
Chronic B cell lymphoproliferative disorders are frequently sensitive to alkylating agents. To assess the glutathione-S-transferases (GSTs) gene expression in B tumoral lymphocytes, possibly responsible for this sensitivity, we developed a sensitive RT-PCR assay for the three isoenzymes GST pi, GST mu and GST alpha mRNA. Normal B and T lymphocytes from 11 blood donors were separated by magnetic beads and tested with this assay. The GST pi was the most abundant transferase, and was detected in all B and T cell samples. GST mu was undetectable ('null' phenotype) in 6/11 normal donors, either in B or T cells. GST alpha was very stable from donor to donor, and was highly correlated between B and T cells of the same individual (P < 0.0001). There is no correlation between the three isoenzymes, and between each isoenzyme and mdr1 gene expression. Twenty-three B lymphoproliferative disorders (20 B-CLL, 3 CD5- chronic lymphoproliferative syndromes) were tested with the same technique. An average decrease of 57% of the GST pi expression was noted in the mononuclear cells of these patients (P < 0.02), with no differences between the untreated and treated cases. The GST alpha and mdr1 mRNA levels did not differ from normal B lymphocytes, but the proportion of patients with no detectable expression of GST mu is lower than in the control (13%). Interestingly, the low content of GST pi in B-CLL could explain the frequent sensitivity of this disease to alkylating agents.
Marie
J P
JP
Laboratoire de Cinétique et de Cultures Cellulaires, Formation de Recherche Associée Claude Bernard sur le Traitement des Hémopathies Malignes, Hôtel Dieu, Paris, France.
Simonin
G
G
Legrand
O
O
Delmer
A
A
Faussat
A M
AM
Lewis
A D
AD
Sikic
B I
BI
Zittoun
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000201:enzymology*; D001483:Base Sequence; D002460:Cell Line; D018432:Drug Resistance, Multiple; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D013601:T-Lymphocytes / Q000201:enzymology*
D007527:Isoenzymes; D012333:RNA, Messenger; D005982:Glutathione Transferase