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Although chemotherapeutic strategies such asCHOP<\/jats:styled-content>have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P\u2010glycoprotein (P\u2010gp) expression. P\u2010gp acts as an energy\u2010dependent efflux pump that excretes drugs from the cytoplasm, resulting in low\u2010intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P\u2010gp expression inEBV<\/jats:styled-content>\u2010positive cells by immunohistochemistry staining in three patients ofEBV<\/jats:styled-content>\u2010T\u2010LPD<\/jats:styled-content>s and the expression was detected in all patients. We also examinedmdr1<\/jats:italic>mRNA<\/jats:styled-content>expression by reverse\u2010transcriptase polymerase\u2010chain reaction (RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>) inEBV<\/jats:styled-content>\u2010positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In fiveEBV<\/jats:styled-content>\u2010T\u2010LPD<\/jats:styled-content>s patients, P\u2010gp function was detected by Rhodamine\u2010123 efflux assay in these cells. The efflux was inhibited by treatment with a P\u2010gp inhibitor, cyclosporine A (CsA). We also examined and detected P\u2010gp expression inEBV<\/jats:styled-content>\u2010positive T\u2010cell linesSNT<\/jats:styled-content>8 andSNT<\/jats:styled-content>16 established fromEBV<\/jats:styled-content>\u2010T\u2010LPD<\/jats:styled-content>s patients, byRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>and western blotting. The function was also detected by Rhodamine\u2010123 efflux in these cell lines. Inhibition and knock down of P\u2010gp by CsA and siRNA<\/jats:styled-content>, respectively, enhanced etoposide\u2010 and doxorubicin\u2010induced cell death in theEBV<\/jats:styled-content>\u2010positive T\u2010cell lines. Finally, we infected the T\u2010cell lineMOLT<\/jats:styled-content>4 withEBV<\/jats:styled-content>, and found thatmdr1<\/jats:italic>mRNA<\/jats:styled-content>expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P\u2010gp expression contributed to the chemoresistance ofEBV<\/jats:styled-content>\u2010T\u2010LPD<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1002\/cam4.494","type":"journal-article","created":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T08:57:43Z","timestamp":1436345863000},"page":"1494-1504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["P\u2010glycoprotein is expressed and causes resistance to chemotherapy inEBV<\/scp>\u2010positive T\u2010cell lymphoproliferative diseases"],"prefix":"10.1002","volume":"4","author":[{"given":"Mayumi","family":"Yoshimori","sequence":"first","affiliation":[{"name":"Department of Hematology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"},{"name":"Department of Laboratory Molecular Genetics of Hematology Graduate School of Health Care Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honami","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Hematology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"},{"name":"Department of Laboratory Molecular Genetics of Hematology Graduate School of Health Care Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken\u2010Ichi","family":"Imadome","sequence":"additional","affiliation":[{"name":"Division of Advanced Medicine for Virus Infections National Research Institute for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morito","family":"Kurata","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Pathology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouhei","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Pathology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Laboratory Molecular Genetics of Hematology Graduate School of Health Care Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Division of Medical Science Department of Virology Medical Research Institute Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyoshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology National Research Institute for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Hematology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Hematology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91744-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198803243181203"},{"key":"e_1_2_7_4_1","first-page":"278","volume-title":"EBV\u2010positive T\u2010cell lymphoproliferative disorders of childhood. 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