{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:46:31Z","timestamp":1791315991324,"version":"4.3.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T00:00:00Z","timestamp":1299542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"RTICS","award":["RD\/06\/0020\/0048"],"award-info":[{"award-number":["RD\/06\/0020\/0048"]}]},{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"crossref","award":["IT-463-07"],"award-info":[{"award-number":["IT-463-07"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"crossref","award":["2006111015"],"award-info":[{"award-number":["2006111015"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Methotrexate (MTX) is an important component of the therapy for childhood acute lymphoblastic leukemia. Treatment with high\u2010dose MTX often causes toxicity, recommending a dose reduction and\/or cessation of treatment. Polymorphisms in genes involved in the MTX metabolism have been associated with toxicity with controversial results. The discrepancies could be due to differences in treatment protocols among studies, small, or non\u2010homogeneous populations or the use of different toxicity criteria. The aim of the present study was to analyze the possible correlation of polymorphisms of genes involved in the MTX metabolism with the toxicity during therapy with the well\u2010established LAL\/SHOP protocol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We analyzed 10 polymorphisms in seven genes (<jats:italic>MTHFR<\/jats:italic>, <jats:italic>TS<\/jats:italic>, <jats:italic>SHMT1<\/jats:italic>, <jats:italic>RFC1<\/jats:italic>, <jats:italic>ABCB1<\/jats:italic>, <jats:italic>ABCG2<\/jats:italic>, and <jats:italic>SLCO1B1<\/jats:italic>) from the MTX metabolism in 115 Spanish pediatric B\u2010ALL patients, using MTX plasma concentration as an objective and quantifiable marker of toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed the suitability of MTX plasma levels as a toxicity marker. We found a statistically significant association between MTX plasma concentration and the <jats:italic>SLCO1B1<\/jats:italic> rs11045879 CC genotype (<jats:italic>P<\/jats:italic>\u2009=\u20090.030). The rs4149081 AA genotype, in the same gene, could also be an indicator for high\u2010MTX plasma concentrations. We did not find any significant association in the other genetic polymorphisms analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Identification of the rs4149081 and rs11045879 <jats:italic>SLCO1B1<\/jats:italic> polymorphisms in children with ALL could be a useful tool for monitoring patients at risk of low\u2010MTX clearance in order to avoid MTX\u2010related toxicity. Pediatr Blood Cancer 2011; 57: 612\u2013619. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.23074","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T19:31:12Z","timestamp":1299612672000},"page":"612-619","source":"Crossref","is-referenced-by-count":113,"title":["Polymorphisms of the SLCO1B1 gene predict methotrexate\u2010related toxicity in childhood acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"57","author":[{"given":"Elixabet","family":"Lopez\u2010Lopez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idoia","family":"Martin\u2010Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Ballesteros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Angeles","family":"Pi\u00f1an","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purificacion","family":"Garcia\u2010Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Navajas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Africa","family":"Garcia\u2010Orad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,8]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07898.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2010.06.020"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60457-2"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(85)90083-X"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610033351408"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1517\/14622416.5.7.819"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.09.017"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.4156"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.24804"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0096-z"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.008326"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-054528"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e318165b25d"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.66"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32833135e9"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902893819"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500332"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2007.02.007"},{"key":"e_1_2_7_20_2","first-page":"1","article-title":"Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy","author":"Erd\u00e9lyi DJ","year":"2007","journal-title":"Pharmacogenomics J"},{"key":"e_1_2_7_21_2","first-page":"pp. 4","volume-title":"Molecular cloning: A laboratory manual","author":"Sambrook J","year":"2001"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.45.120403.100018"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01128.x"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000198269.61948.90"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2606"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10245330701448479"},{"key":"e_1_2_7_29_2","first-page":"1113","article-title":"Folate cycle gene variants and chemotherapy toxicity in pediatric patients with acute lymphoblastic leukemia","volume":"91","author":"Costea I","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103792200"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.024315"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.197"}],"container-title":["Pediatric Blood &amp; 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