[Significance of functional assay of multidrug resistance for prediction of chemotherapy outcomes in acute leukemia].

BACKGROUND & OBJECTIVE: It is well known that the multidrug resistance (MDR) efflux protein, P-glycoprotein (P-gp), plays an important role in mediating MDR in acute leukemia. Several studies have shown that the expression level of P-gp and its encoding gene MDR1 mRNA level are associated with the response of chemotherapy. But what we have observed in clinical practice is in contradiction with this. Besides, several recent reports have shown that the results of MDR functional assay are more predictive of chemotherapy outcomes than P-gp expression level. To examine the prognostic value of P-gp expression and MDR functional assay in acute leukemia, the authors determined the expression levels of P-gp and MDR function in 24 patients with de novo acute leukemia. The predictive value of MDR functional assay for chemotherapy outcomes was discussed.

METHODS

The expression percentile of P-gp and the mean fluorescence intensity ratio of rhodamine 123 efflux assay [MIR(RE)] and intracellular daunorubicin accumulation assay [MIR(IDA)] of patients' leukemic cell samples were determined with flow cytometry. The results of remission (CR) and non-remission (NR) patients were compared. Correlative analysis was made between test results and chemotherapy outcomes.

RESULTS

The expression levels of P-gp were not significantly different between CR and NR patients (2.16%+/-2.42% versus 15.02%+/-25.88%, P=0.114). But the MIR (RE) (1.16+/-0.38 versus 1.43+/-0.26, P=0.045) and MIR (IDA) (1.02+/-0.05 versus 1.47+/-0.44,P=0.005) were both significantly lower in CR patients than those in NR patients. Both MIR (RE) (r=0.590, P=0.006) and MIR (IDA) (r=0.867, P=0.000) were significantly correlated with chemotherapy outcomes. But the expression level of P-gp was not correlated with the chemotherapy results.

CONCLUSION

The determination of MIR value of MDR functional assay is more valuable than P-gp expression level in predicting chemotherapy outcomes.