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The functionally relevant characteristic of MDR cells is a defect in drug accumulation that can be restored by agents which inhibit the P\u2010glycoprotein pump. The purpose of our study was to find out whether Pglycoprotein inhibitors could increase the daunorubicin (DNR) accumulation in acute myelocytic leukemia (AML) cells, overexpressing the <jats:italic>mdrl<\/jats:italic> gene. Using dot blot analysis with an <jats:italic>mdrl<\/jats:italic>\u2010specific <jats:italic>cDNA<\/jats:italic> probe, we identified leukemic cell samples, obtained from chemotherapy\u2010resistant AML patients, that had relatively high levels of <jats:italic>mdrl<\/jats:italic> expression. These leukemic cells showed a reduced ability to accumulate DNR <jats:italic>in vitro<\/jats:italic>, as quantitated by flow cytometry. Addition of cyclosporin\u2010A (Cy\u2010A), a drug known to inhibit the P\u2010glycoprotein pump, to the incubation medium resulted in an increase (up to 60%) in steady\u2010state drug uptake by the leukemic cells. The degree of Cy\u2010A\u2010induced increase in drug accumulation in the leukemic cells correlated approximately with the level of overexpression of the <jats:italic>mdrl<\/jats:italic> gene. Our data indicate that Cy\u2010A is a good candidate for combination chemotherapy with cytotoxic drugs in clinical trials, aimed at the treatment of drug resistance in AML.<\/jats:p>","DOI":"10.1002\/ijc.2910450210","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T21:59:30Z","timestamp":1171922370000},"page":"263-268","source":"Crossref","is-referenced-by-count":96,"title":["Overexpression of the <i>MDRL<\/i> gene in blast cells from patients with acute myelocytic leukemia is associated with decreased anthracycline accumulation that can be restored by cyclosporin\u2010A"],"prefix":"10.1002","volume":"45","author":[{"given":"Kees","family":"Nooter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Oostrum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Herweijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ton","family":"Hagenbeek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinko","family":"Valerio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/BF02934930","article-title":"Sensitivity and resistance to chemotherapy in acute leukemia: correlation with in vitro drug uptake and lack of potentiation by verapamil","volume":"4","author":"Andersson B.","year":"1987","journal-title":"Med. 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