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• W2095081036 abstract "The efficacy of verapamil and cyclosporine A as modulators of P-glycoprotein, the multidrug resistance (MDR1) gene product, was studied in leukemic blast cells from 56 patients with de novo acute myeloid leukemia (AML) in vitro. Rhodamine123 dye-efflux was measured flow cytometrically as a cellular parameter reflecting P-glycoprotein activity. While dye-efflux was measurable in 34 of the cases, the capacity of the P-glycoprotein inhibitors varied substantially among patients. In 23 patients, P-glycoprotein function was completely inhibited by the resistance modulators, whereas in 17 patients neither verapamil nor cyclosporine had any reverting effect on dye-efflux at concentrations even 10-times higher than achievable in vivo. Cells with a drug-sensitive rhodamine123-pump effluxed more efficiently (p=0.0016) and contained significantly higher levels of MDR1 specific RNA transcripts (p=0.0002), as determined by quantitative PCR, than cells exhibiting an efflux process that could not be inhibited. However, flow cytometric evaluation of the staining of gated blast cells with the anti-P-glycoprotein antibody, 4E3.16, revealed no difference in P-glycoprotein expression between modulator-sensitive and -insensitive cases (p=0.86), indicating disproportionate translation of MDRI mRNA. In leukemic cell populations with increased P-glycoprotein function that could be inhibited, significantly more blasts expressed the progenitor cell antigen, CD34 (median 83%), than was the case in leukemias with P-glycoprotein activity that could not be inhibited (median 7%) (p=0.0001). The present study demonstrates that a substantial fraction of AML patients constitutively display a drug-efflux mechanism suggestive of P-glycoprotein activity. However, in many of those patients rhodamine123-efflux from blast cells in vitro was not sensitive to classical P-glycoprotein inhibitors" @default.
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• W2095081036 date "1995-03-01" @default.
• W2095081036 modified "2023-10-16" @default.
• W2095081036 title "Modulation of multidrug resistance in de novo adult acute myeloid leukemia: Variable efficacy of reverting agents in vitro" @default.
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• W2095081036 doi "https://doi.org/10.1016/0268-960x(95)90039-x" @default.
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