GLUTATHIONE-S-TRANSFERASE-PI, GLUTATHIONE-S-TRANSFERASE-ALPHA, GLUTATHIONE-S-TRANSFERASE-MU AND GLUTATHIONE-S-TRANSFERASE-MDR1 MESSENGER-RNA 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 thi s sensitivity, we developed a sensitive RT-PCR assay for the three iso enzymes 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 dete cted in all B and T cell samples. GST mu was undetectable ('null' phen otype) in 6/11 normal donors, either in B or T cells. GST alpha was ve ry 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 sa me 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 d ifferences between the untreated and treated cases. The GST alpha and mdr1 mRNA levels did not differ from normal B lymphocytes, but the pro portion of patients with no detectable expression of GST mu is lower t han in the control (13%). Interestingly, the low content of GST pi in B-CLL could explain the frequent sensitivity of this disease to alkyla ting agents.