ANALYSIS OF MDR1 AND MDR3 MULTIDRUG-RESISTANCE GENE-EXPRESSION AND AMPLIFICATION IN CONSECUTIVE SAMPLES IN PATIENTS WITH ACUTE LEUKEMIAS

White blood cells from a total of 19 patients diagnosed as having acut e lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed ( 36 samples) for amplification and expression of the mdr1 and mdr3 gene s, Nine of the patients had samples analysed at presentation and at su bsequent stages of the disease (24 samples, including 4 at second rela pse), Patients received standard MRC UK Trial remission-induction trea tment protocols appropriate to disease and age. No amplification of ei ther the mdr1 or mdr3 gene was found in any of the samples, and neithe r were mdr3 transcripts detected by dot-blot analysis using gene-speci fic probes. Transcripts of the mdr1 gene were found in only 2 ALL samp les (of 10). However, mdr1 transcripts were detected in all AML patien ts and there was a significant increase in the transcript levels in th ese patients who went on to first and second relapse, compared with le vels measured at presentation (P < 0.001), The results support the hyp othesis that P-glycoprotein-mediated drug resistance may be a signific ant factor in tumour cell resistance to chemotherapy at relapse follow ing initial induction-remission therapy for acute myeloid leukemia.