{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T14:41:36Z","timestamp":1700318496773},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,10,30]],"date-time":"2002-10-30T00:00:00Z","timestamp":1035936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In vitro resistance to anthracyclines is thought to be a poor prognosis in achieving long\u2010term remission in patients with acute lymphoblastic leukemia (ALL). Expression of a multidrug resistance gene (<jats:italic>mdr1<\/jats:italic>) that codes for 170 Kd transmembrane glycoprotein is responsible for conferring resistance to malignant cells to anthracyclines. The t(9:22) translocation, resulting in <jats:italic>bcr\u2010abl<\/jats:italic> fusion gene, is commonly found in B\u2010lineage ALL and is known to be a poor prognostic factor for long\u2010term remission. To investigate whether resistance to anthracyclines contributes to poor prognosis in <jats:italic>bcr\u2010abl<\/jats:italic>\u2010positive ALL, we studied daunorubicin sensitivity by an in vitro colorimetric methyl tetrazolium (MTT) assay in B\u2010lineage ALL patients who were <jats:italic>bcr\u2010abl<\/jats:italic>\u2010positive and compared them with the B\u2010lineage, age\u2010matched <jats:italic>bcr\u2010abl<\/jats:italic>\u2010negative group. We also looked for and compared the presence of <jats:italic>mdr1<\/jats:italic> gene expression in these two groups of patients by RT\u2010PCR. Of the 46 patients included in the study, 16 (34.7%) were positive for the <jats:italic>bcr\u2010abl<\/jats:italic> fusion gene. <jats:italic>mdr1<\/jats:italic> gene expression was seen in 14 of these 46 patients (30.4%). However, the expression of the <jats:italic>mdr1<\/jats:italic> gene was relatively lower in the <jats:italic>bcr\u2010abl<\/jats:italic>\u2010positive group (3 out of 16, 18.7%) compared to the <jats:italic>bcr\u2010abl<\/jats:italic>\u2010negative group (11 out of 30, 36.6%). The median LD<jats:sub>50<\/jats:sub> of daunorubicin (concentration lethal to 50% of the leukemic blasts) differed significantly between <jats:italic>bcr\u2010abl<\/jats:italic>\u2010positive and \u2010negative patients (<jats:italic>P<\/jats:italic> = 0.018). This in vitro study suggests that <jats:italic>bcr\u2010abl<\/jats:italic>\u2010positive ALL is relatively resistant to daunorubicin, but this resistance is not mediated through <jats:italic>mdr1<\/jats:italic> gene expression. Am. J. Hematol. 71:172\u2013176, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.10212","type":"journal-article","created":{"date-parts":[[2002,10,31]],"date-time":"2002-10-31T18:20:30Z","timestamp":1036088430000},"page":"172-176","source":"Crossref","is-referenced-by-count":5,"title":["Resistance of <i>bcr\u2010abl<\/i>\u2010positive acute lymphoblastic leukemia to daunorubicin is not mediated by <i>mdr1<\/i> Gene Expression"],"prefix":"10.1002","volume":"71","author":[{"given":"Mamta","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil","family":"Dabadghao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10,30]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1056\/NEJM200004063421402","article-title":"Outcome of treatment in children with Philadelphia chromosome positive acute lymphoblastic leukaemia","volume":"342","author":"Arico M","journal-title":"N Engl J Med"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.bi.58.070189.001033","article-title":"The biochemistry of p\u2010glycoprotein mediated multidrug resistance","volume":"58","author":"Endicott JA","year":"1989","journal-title":"Annu Rev Biochem"},{"key":"e_1_2_1_4_2","first-page":"1870","article-title":"Expression of the multidrug resistance P glycoprotein in newly diagnosed adult acute lymphoblastic leukaemia: absence of correlation with response to treatment","volume":"9","author":"Wattel E","year":"1995","journal-title":"Leukaemia"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4811-9_1"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.5414\/CPP38094"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690133"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402079"},{"key":"e_1_2_1_9_2","first-page":"186","article-title":"An optimized multiplex polymerase chain reaction for detection of bcr\u2010abl fusion mRNA in hematological disorders","volume":"8","author":"Cross NCP","year":"1994","journal-title":"Leukaemia"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002770050388"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(88)90294-7"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401129"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02969.x"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.17.1352"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400668"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199809)23:1<44::AID-GCC7>3.0.CO;2-6"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.10212","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.10212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T14:18:27Z","timestamp":1700317107000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.10212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10,30]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["10.1002\/ajh.10212"],"URL":"https:\/\/doi.org\/10.1002\/ajh.10212","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,10,30]]}}}