{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:51:36Z","timestamp":1770508296490,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":5938,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1990,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Typical multidrug resistance in human and animal cell lines is caused by overactivity of an unidirectional transmembrane drug efflux pump, encoded by the MDR genes, called <jats:italic>mdr<\/jats:italic> genes in mice and humans and <jats:italic>pgp<\/jats:italic> genes in hamsters. In humans, two <jats:italic>mdr<\/jats:italic> genes, <jats:italic>mdr<\/jats:italic>1 and <jats:italic>mdr<\/jats:italic>3, with approximately 80% nucleotide homology, have been identified. There is increasing evidence that overexpression of the <jats:italic>mdr<\/jats:italic>1 gene plays a role in resistance to anticancer agents in specific tumor types. However, currently no data are available on a possible role for <jats:italic>mdr<\/jats:italic>3 in drug resistance. Here we report high levels of expression of <jats:italic>mdr<\/jats:italic>3 gene sequences in leukemic cells from 6 out of 6 patients with prolymphocytic leukemia (PLL). No <jats:italic>mdr<\/jats:italic>1 expression was detected in 5 out of 6 of these samples, whereas a low level of <jats:italic>mdr<\/jats:italic>1 expression was found in a sample from one PLL patient in the course of transformation to non\u2010Hodgkin's lymphoma. Except for this patient, all other PLL cases studied had not received prior chemotherapy. <jats:italic>In vitro<\/jats:italic> drug uptake studies showed that daunorubicin accumulation in PLL cells was increased by cyclosporin A. Since cyclosporin A is an inhibitor of the <jats:italic>mdr<\/jats:italic>1\u2010encoded P\u2010glycoprotein drug pump, these data suggest that in PLL cells <jats:italic>mdr<\/jats:italic>3 also codes for a drug efflux pump. Our findings could partly explain the primary refractoriness of PLL to chemotherapy.<\/jats:p>","DOI":"10.1002\/ijc.2910450409","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T21:58:12Z","timestamp":1171922292000},"page":"626-631","source":"Crossref","is-referenced-by-count":46,"title":["Expression of the <i>mdr<\/i>3 gene in prolymphocytic leukemia: Association with cyclosporin\u2010a\u2010induced increase in drug accumulation"],"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":"Arjenne","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Oostrum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ton","family":"Boersma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Herweijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinko","family":"Valerjo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Hagemeijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Baas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1980.tb06030.x"},{"key":"e_1_2_1_3_1","first-page":"87","article-title":"Mechanisms of multidrug resistance","volume":"948","author":"Bradley G.","year":"1988","journal-title":"Biochim. biophys. 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