Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma.

We have quantitated the levels of mRNAs in bone marrow samples from patients with multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3 (which can also inactivate a wide variety of cytotoxic drugs) and examined the relationship between the levels of expression of these genes and response to subsequent chemotherapy. From a total of 47 patients, 37 were treated with chemotherapy with 34 evaluable for response. Twenty-nine of the patients treated had not received any treatment prior to the marrow sampling while eight had previously received chemotherapy. Patients who failed to respond to initial chemotherapy had significantly higher levels of mdr1 than patients who responded (P = 0.01). In the total myeloma patient data set, mRNA levels for mdr1 and GST-2 were significantly correlated (Spearman rank correlation coefficient (r) = 0.54, P = 0.0004) as were expression levels of GST-2 with GST-3 (r = 0.43, P = 0.017). GST-3 and mdr1 levels were more weekly associated (r = 0.16, P = 0.4). These data would suggest a significant relationship between failure of chemotherapy in multiple myeloma patients and increases in expression of the mdr1 gene together with other genes whose products will generate additional mechanisms of resistance to chemotherapeutic agents.