MULTIDRUG-RESISTANCE GENE (MDR1) RNA LEVELS IN RELATION TO P-GLYCOPROTEIN CONTENT OF LEUKEMIC-CELLS FROM PATIENTS WITH ACUTE-LEUKEMIA

The clinical relevance of multidrug resistance gene (mdr1) expression in tumor cells remains largely unclear. Conflicting results regarding mdr1 gene expression and clinical outcome have been obtained. Little i s known about regulation of mdr1 gene expression, and the conflicting results might be explained by the fact that mdr1 RNA levels do not ref lect expression at the protein level. The aim of the present study was to investigate the relationship between mdr1 RNA levels and P-glycopr otein (Pgp) content of leukemic cells from patients with acute myeloge nous or lymphocytic leukemia. Mdr1 RNA levels were determined by a qua ntitative RNA-RNA solution hybridization method, and Pgp by Western bl ot technique with enhanced chemiluminescence for immunodetection. Pgp was detected in 14/14 leukemic cell samples while mdr1 RNA was detecta ble (>0.15 copies/cell) in cells from only six out of the 14 patients. Mdr1 RNA levels did not correlate with the Pgp content of leukemic ce lls (r=0.284, p=0.306). Relapsed leukemias had significantly (p=0.016) higher levels of Pgp than de novo untreated leukemias (the mean and S D optical density units were 0.56+/-0.18 and 0.25+/-0.17 respectively) while no difference was found in RNA levels. The findings support pos t-transcriptional level regulation of mdr1 gene expression and stress the importance of accurate determinations of the Pgp content of tumor cells in studies of the relationship between mdr1 gene expression and clinical outcome.