ANALYSIS OF MDR-1 GENE-EXPRESSION IN HUMAN LEUKEMIC-CELLS BY QUANTITATIVE COMPETITIVE PCR

The ability to recognize the acquisition of multidrug resistance (MDR) in leukemia patients would improve our ability to predict the respons iveness of patients to chemotherapy. To quantitate the degree of MDR a cquisition, we determined the amount of mdr-1 mRNA in leukemic cells f rom patients by competitive polymerase chain reaction (PCR) analysis. Twenty-one patients including 12 patients prior to treatment and nine relapsed patients with acute myelogenous or lymphoblastic leukemia wer e examined. The amount of mdr-1 gene expression in K562, K562/ADR(500) cells and their mixtures showed a proportional correlation between th e ratio of resistant to non-resistant cells and the amount of the mdr- 1 gene. Mean mdr-1 gene expression in relapsed patients was greater th an that in pretreatment patients. Patients refractory to chemotherapy (NR) showed higher levels of mdr-1 gene expression than the patients w ho achieved complete remission (CR). Because of the wide variations in values, no statistical differences were observed between pretreatment and relapsed patients, or CR and NR patients. These results suggest t hat the competitive PCR technique is a reliable method to quantitative ly determine mdr-1 gene expression, but it may be difficult to predict responsiveness to chemotherapy by using this technique alone.