PMID: 7540903Mar 1, 1995Paper

Modulation of multidrug resistance in de novo adult acute myeloid leukemia: variable efficacy of reverting agents in vitro. Eastern Cooperative Oncology Group

Blood Reviews
E PaiettaP H Wiernik

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 3/4 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 = 0.8...Continue Reading

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Citations

Sep 1, 1995·Medical Oncology·E Paietta
Mar 1, 1997·Medical Oncology·E Paietta
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H S ChanV Ling
Jul 1, 2009·Journal of Pediatric Hematology/oncology·Jacek BrozekJacek M Witkowski
Mar 17, 2007·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·R J MorganJ H Doroshow
Aug 7, 2002·Leukemia Research·Bin ZhangKe-Fu Wu
Mar 17, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter L GreenbergJacob M Rowe
Oct 25, 2003·Oncogene·Sarah J FreemantleEthan Dmitrovsky
Feb 3, 2011·Blood·Jae H ParkMartin S Tallman
Dec 21, 2002·British Journal of Haematology·Yasushi MiyazakiUNKNOWN Japan Adult Leukaemia Study Group

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