{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:33:47Z","timestamp":1792514027928,"version":"4.5.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacogenomics J"],"published-print":{"date-parts":[[2015,6]]},"DOI":"10.1038\/tpj.2014.63","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T10:59:42Z","timestamp":1414493982000},"page":"248-254","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia"],"prefix":"10.1038","volume":"15","author":[{"given":"M A H","family":"den Hoed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Lopez-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M L","family":"te Winkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Tissing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J D E","family":"de Rooij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gutierrez-Camino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Garcia-Orad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"den Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Pieters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M F","family":"Pluijm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M M","family":"van den Heuvel-Eibrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,11,4]]},"reference":[{"key":"BFtpj201463_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S1470-2045(13)70548-5","volume":"15","author":"G Gatta","year":"2014","unstructured":"Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Clavel J et al. Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5-a population-based study. Lancet Oncol 2014; 15: 35\u201347.","journal-title":"Lancet Oncol"},{"key":"BFtpj201463_CR2","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1200\/JCO.2010.30.7405","volume":"29","author":"CH Pui","year":"2011","unstructured":"Pui CH, Carroll WL, Meshinchi S, Arceci RJ . Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol 2011; 29: 551\u2013565.","journal-title":"J Clin Oncol"},{"key":"BFtpj201463_CR3","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/leu.2009.258","volume":"24","author":"WA Kamps","year":"2010","unstructured":"Kamps WA, van der Pal-de Bruin KM, Veerman AJ, Fiocco M, Bierings M, Pieters R . Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984\u20132004. Leukemia 2010; 24: 309\u2013319.","journal-title":"Leukemia"},{"key":"BFtpj201463_CR4","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1002\/cncr.20152","volume":"100","author":"KR Crews","year":"2004","unstructured":"Crews KR, Liu T, Rodriguez-Galindo C, Tan M, Meyer WH, Panetta JC et al. High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer 2004; 100: 1724\u20131733.","journal-title":"Cancer"},{"key":"BFtpj201463_CR5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1124\/pr.110.002857","volume":"63","author":"M Niemi","year":"2011","unstructured":"Niemi M, Pasanen MK, Neuvonen PJ . Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev 2011; 63: 157\u2013181.","journal-title":"Pharmacol Rev"},{"key":"BFtpj201463_CR6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev-nutr-072610-145133","volume":"31","author":"R Zhao","year":"2011","unstructured":"Zhao R, Diop-Bove N, Visentin M, Goldman ID . Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr 2011; 31: 177\u2013201.","journal-title":"Annu Rev Nutr"},{"key":"BFtpj201463_CR7","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1007\/s00228-013-1521-9","volume":"69","author":"P Wennerstrand","year":"2013","unstructured":"Wennerstrand P, Martensson LG, Soderhall S, Zimdahl A, Appell ML . Methotrexate binds to recombinant thiopurine S-methyltransferase and inhibits enzyme activity after high-dose infusions in childhood leukaemia. Eur J Clin Pharmacol 2013; 69: 1641\u20131649.","journal-title":"Eur J Clin Pharmacol"},{"key":"BFtpj201463_CR8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1517\/14622416.5.7.819","volume":"5","author":"M Krajinovic","year":"2004","unstructured":"Krajinovic M, Moghrabi A . Pharmacogenetics of methotrexate. Pharmacogenomics 2004; 5: 819\u2013834.","journal-title":"Pharmacogenomics"},{"key":"BFtpj201463_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/pbc.20242","volume":"44","author":"Y Ravindranath","year":"2005","unstructured":"Ravindranath Y . Down syndrome and leukemia: new insights into the epidemiology, pathogenesis, and treatment. Pediatr Blood Cancer 2005; 44: 1\u20137.","journal-title":"Pediatr Blood Cancer"},{"key":"BFtpj201463_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/76088","volume":"25","author":"H Witt","year":"2000","unstructured":"Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000; 25: 213\u2013216.","journal-title":"Nat Genet"},{"key":"BFtpj201463_CR11","unstructured":"Assembly WMAG. The Declaration of Helsinki \u2014 Sixth Revision. Helsinki, Finland, 2008."},{"key":"BFtpj201463_CR12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/S1053-4296(03)00031-6","volume":"13","author":"A Trotti","year":"2003","unstructured":"Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13: 176\u2013181.","journal-title":"Semin Radiat Oncol"},{"key":"BFtpj201463_CR13","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1046\/j.1472-8206.2002.00086.x","volume":"16","author":"A Rousseau","year":"2002","unstructured":"Rousseau A, Marquet P . Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugs. Fundam Clin Pharmacol 2002; 16: 253\u2013262.","journal-title":"Fundam Clin Pharmacol"},{"key":"BFtpj201463_CR14","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1515\/CCLM.2006.178","volume":"44","author":"V Ducros","year":"2006","unstructured":"Ducros V, Belva-Besnet H, Casetta B, Favier A . A robust liquid chromatography tandem mass spectrometry method for total plasma homocysteine determination in clinical practice. Clin Chem Lab Med 2006; 44: 987\u2013990.","journal-title":"Clin Chem Lab Med"},{"key":"BFtpj201463_CR15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1097\/00008571-200204000-00002","volume":"12","author":"W Urano","year":"2002","unstructured":"Urano W, Taniguchi A, Yamanaka H, Tanaka E, Nakajima H, Matsuda Y et al. Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics 2002; 12: 183\u2013190.","journal-title":"Pharmacogenetics"},{"key":"BFtpj201463_CR16","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1002\/1529-0131(200111)44:11<2525::AID-ART432>3.0.CO;2-B","volume":"44","author":"AE van Ede","year":"2001","unstructured":"van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA et al. The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum 2001; 44: 2525\u20132530.","journal-title":"Arthritis Rheum"},{"key":"BFtpj201463_CR17","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/01.mph.0000198269.61948.90","volume":"28","author":"N Shimasaki","year":"2006","unstructured":"Shimasaki N, Mori T, Samejima H, Sato R, Shimada H, Yahagi N et al. Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma. J Pediatr Hematol Oncol 2006; 28: 64\u201368.","journal-title":"J Pediatr Hematol Oncol"},{"key":"BFtpj201463_CR18","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1038\/leu.2008.66","volume":"22","author":"L Huang","year":"2008","unstructured":"Huang L, Tissing WJ, de Jonge R, van Zelst BD, Pieters R . Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia 2008; 22: 1798\u20131800.","journal-title":"Leukemia"},{"key":"BFtpj201463_CR19","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1158\/0008-5472.CAN-04-2606","volume":"65","author":"R Aplenc","year":"2005","unstructured":"Aplenc R, Thompson J, Han P, La M, Zhao H, Lange B et al. Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia. Cancer Res 2005; 65: 2482\u20132487.","journal-title":"Cancer Res"},{"key":"BFtpj201463_CR20","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00277-005-0072-2","volume":"85","author":"K Seidemann","year":"2006","unstructured":"Seidemann K, Book M, Zimmermann M, Meyer U, Welte K, Stanulla M et al. MTHFR 677 (C\u2014&gt;T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95. Ann Hematol 2006; 85: 291\u2013300.","journal-title":"Ann Hematol"},{"key":"BFtpj201463_CR21","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1182\/blood-2004-12-4941","volume":"106","author":"R de Jonge","year":"2005","unstructured":"de Jonge R, Hooijberg JH, van Zelst BD, Jansen G, van Zantwijk CH, Kaspers GJ et al. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. Blood 2005; 106: 717\u2013720.","journal-title":"Blood"},{"key":"BFtpj201463_CR22","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0065-2571(96)00012-X","volume":"37","author":"G Jansen","year":"1997","unstructured":"Jansen G, Mauritz RM, Assaraf YG, Sprecher H, Drori S, Kathmann I et al. Regulation of carrier-mediated transport of folates and antifolates in methotrexate-sensitive and-resistant leukemia cells. Adv Enzyme Regul 1997; 37: 59\u201376.","journal-title":"Adv Enzyme Regul"},{"key":"BFtpj201463_CR23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/FPC.0b013e32835c3b24","volume":"23","author":"E Lopez-Lopez","year":"2013","unstructured":"Lopez-Lopez E, Ballesteros J, Pinan MA, Sanchez de Toledo J, Garcia de Andoin N, Garcia-Miguel P et al. Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia. Pharmacogenet Genomics 2013; 23: 53\u201361.","journal-title":"Pharmacogenet Genomics"},{"key":"BFtpj201463_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/gr.129668.111","volume":"22","author":"LB Ramsey","year":"2012","unstructured":"Ramsey LB, Bruun GH, Yang W, Trevino LR, Vattathil S, Scheet P et al. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 2012; 22: 1\u20138.","journal-title":"Genome Res"},{"key":"BFtpj201463_CR25","doi-asserted-by":"publisher","first-page":"5145","DOI":"10.1182\/blood-2013-01-480335","volume":"121","author":"S Radtke","year":"2013","unstructured":"Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Moricke A et al. Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood 2013; 121: 5145\u20135153.","journal-title":"Blood"},{"key":"BFtpj201463_CR26","doi-asserted-by":"publisher","first-page":"7403","DOI":"10.1038\/sj.onc.1206944","volume":"22","author":"E Krynetski","year":"2003","unstructured":"Krynetski E, Evans WE . Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene 2003; 22: 7403\u20137413.","journal-title":"Oncogene"},{"key":"BFtpj201463_CR27","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.cccn.2004.11.019","volume":"354","author":"PH Griffioen","year":"2005","unstructured":"Griffioen PH, de Jonge R, van Zelst BD, Montserrate Brouns R, Lindemans J . Detection and allele-frequencies of the 833T&gt;C, 844ins68 and a novel mutation in the cystathionine beta-synthase gene. Clin Chim Acta 2005; 354: 191\u2013194.","journal-title":"Clin Chim Acta"},{"key":"BFtpj201463_CR28","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/bioinformatics\/btl268","volume":"22","author":"X Sole","year":"2006","unstructured":"Sole X, Guino E, Valls J, Iniesta R, Moreno V . SNPStats: a web tool for the analysis of association studies. Bioinformatics 2006; 22: 1928\u20131929.","journal-title":"Bioinformatics"},{"key":"BFtpj201463_CR29","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1037\/0022-3514.51.6.1173","volume":"51","author":"RM Baron","year":"1986","unstructured":"Baron RM, Kenny DA . The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986; 51: 1173\u20131182.","journal-title":"J Pers Soc Psychol"},{"key":"BFtpj201463_CR30","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","volume":"21","author":"JC Barrett","year":"2005","unstructured":"Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263\u2013265.","journal-title":"Bioinformatics"},{"key":"BFtpj201463_CR31","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.3324\/haematol.2009.019778","volume":"95","author":"TD Buitenkamp","year":"2010","unstructured":"Buitenkamp TD, Mathot RA, de Haas V, Pieters R, Zwaan CM . Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia. Haematologica 2010; 95: 1106\u20131113.","journal-title":"Haematologica"},{"key":"BFtpj201463_CR32","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3109\/10428194.2011.563883","volume":"52","author":"SG Liu","year":"2011","unstructured":"Liu SG, Li ZG, Cui L, Gao C, Li WJ, Zhao XX . Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population. Leuk Lymphoma 2011; 52: 1030\u20131040.","journal-title":"Leuk Lymphoma"},{"key":"BFtpj201463_CR33","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1007\/s00228-011-1046-z","volume":"67","author":"B Faganel Kotnik","year":"2011","unstructured":"Faganel Kotnik B, Grabnar I, Bohanec Grabar P, Dolzan V, Jazbec J . Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma. Eur J Clin Pharmacol 2011; 67: 993\u20131006.","journal-title":"Eur J Clin Pharmacol"},{"key":"BFtpj201463_CR34","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/labinvest.3780067","volume":"80","author":"V Witko-Sarsat","year":"2000","unstructured":"Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L . Neutrophils: molecules, functions and pathophysiological aspects. Lab Invest 2000; 80: 617\u2013653.","journal-title":"Lab Invest"},{"key":"BFtpj201463_CR35","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1600-0609.2008.01128.x","volume":"81","author":"PB van Kooten Niekerk","year":"2008","unstructured":"van Kooten Niekerk PB, Schmiegelow K, Schroeder H . Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate. Eur J Haematol 2008; 81: 391\u2013398.","journal-title":"Eur J Haematol"},{"key":"BFtpj201463_CR36","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3324\/haematol.10232","volume":"92","author":"P Niscola","year":"2007","unstructured":"Niscola P, Romani C, Cupelli L, Scaramucci L, Tendas A, Dentamaro T et al. Mucositis in patients with hematologic malignancies: an overview. Haematologica 2007; 92: 222\u2013231.","journal-title":"Haematologica"},{"key":"BFtpj201463_CR37","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1365-2354.2007.00843.x","volume":"17","author":"KK Cheng","year":"2008","unstructured":"Cheng KK . Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea\/vomiting and oral mucositis in children with cancer. Eur J Cancer Care (Engl) 2008; 17: 306\u2013311.","journal-title":"Eur J Cancer Care (Engl)"},{"key":"BFtpj201463_CR38","doi-asserted-by":"publisher","first-page":"584","DOI":"10.5414\/CPP46584","volume":"46","author":"T Maiguma","year":"2008","unstructured":"Maiguma T, Hayashi Y, Ueshima S, Kaji H, Egawa T, Chayama K et al. Relationship between oral mucositis and high-dose methotrexate therapy in pediatric acute lymphoblastic leukemia. Int J Clin Pharmacol Ther 2008; 46: 584\u2013590.","journal-title":"Int J Clin Pharmacol Ther"},{"key":"BFtpj201463_CR39","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1172\/JCI118409","volume":"97","author":"E Masson","year":"1996","unstructured":"Masson E, Relling MV, Synold TW, Liu Q, Schuetz JD, Sandlund JT et al. Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate. J Clin Invest 1996; 97: 73\u201380.","journal-title":"J Clin Invest"},{"key":"BFtpj201463_CR40","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1200\/JCO.2010.32.5340","volume":"29","author":"TS Mikkelsen","year":"2011","unstructured":"Mikkelsen TS, Sparreboom A, Cheng C, Zhou Y, Boyett JM, Raimondi SC et al. Shortening infusion time for high-dose methotrexate alters antileukemic effects: a randomized prospective clinical trial. J Clin Oncol 2011; 29: 1771\u20131778.","journal-title":"J Clin Oncol"},{"key":"BFtpj201463_CR41","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1002\/art.20278","volume":"50","author":"JM Kremer","year":"2004","unstructured":"Kremer JM . Toward a better understanding of methotrexate. Arthritis Rheum 2004; 50: 1370\u20131382.","journal-title":"Arthritis Rheum"},{"key":"BFtpj201463_CR42","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1093\/jn\/136.1.153","volume":"136","author":"V Ganji","year":"2006","unstructured":"Ganji V, Kafai MR . Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002. J Nutr 2006; 136: 153\u2013158.","journal-title":"J Nutr"},{"key":"BFtpj201463_CR43","volume-title":"Folate in Health and Disease","author":"LB Bailey","year":"2010","unstructured":"Bailey LB . Folate in Health and Disease, 2nd edn. Taylor & Francis, 2010."},{"key":"BFtpj201463_CR44","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1002\/art.38113","volume":"65","author":"MC de Rotte","year":"2013","unstructured":"de Rotte MC, de Jong PH, Pluijm SM, Calasan MB, Barendregt PJ, van Zeben D et al. Association of low baseline levels of erythrocyte folate with treatment nonresponse at three months in rheumatoid arthritis patients receiving methotrexate. Arthritis Rheum 2013; 65: 2803\u20132813.","journal-title":"Arthritis Rheum"},{"key":"BFtpj201463_CR45","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1093\/ajcn\/68.4.866","volume":"68","author":"YI Kim","year":"1998","unstructured":"Kim YI, Fawaz K, Knox T, Lee YM, Norton R, Arora S et al. Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps. Am J Clin Nutr 1998; 68: 866\u2013872.","journal-title":"Am J Clin Nutr"},{"key":"BFtpj201463_CR46","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1634\/theoncologist.4-4-340","volume":"4","author":"DS Goodsell","year":"1999","unstructured":"Goodsell DS . The molecular perspective: methotrexate. Oncologist 1999; 4: 340\u2013341.","journal-title":"Oncologist"},{"key":"BFtpj201463_CR47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.drup.2006.09.001","volume":"9","author":"YG Assaraf","year":"2006","unstructured":"Assaraf YG . The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. Drug Resist Updat 2006; 9: 227\u2013246.","journal-title":"Drug Resist Updat"},{"key":"BFtpj201463_CR48","first-page":"4418","volume":"36","author":"HM Pinedo","year":"1976","unstructured":"Pinedo HM, Zaharko DS, Bull JM, Chabner BA . The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. Cancer Res 1976; 36: 4418\u20134424.","journal-title":"Cancer Res"},{"key":"BFtpj201463_CR49","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3109\/08880019609030842","volume":"13","author":"C Rask","year":"1996","unstructured":"Rask C, Albertioni F, Schroder H, Peterson C . Oral mucositis in children with acute lymphoblastic leukemia after high-dose methotrexate treatment without delayed elimination of methotrexate: relation to pharmacokinetic parameters of methotrexate. Pediatr Hematol Oncol 1996; 13: 359\u2013367.","journal-title":"Pediatr Hematol Oncol"},{"key":"BFtpj201463_CR50","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1002\/art.21295","volume":"52","author":"D Khanna","year":"2005","unstructured":"Khanna D, Park GS, Paulus HE, Simpson KM, Elashoff D, Cohen SB et al. Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies. Arthritis Rheum 2005; 52: 3030\u20133038.","journal-title":"Arthritis Rheum"},{"key":"BFtpj201463_CR51","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1373\/clinchem.2005.061150","volume":"52","author":"J Sterba","year":"2006","unstructured":"Sterba J, Dusek L, Demlova R, Valik D . Pretreatment plasma folate modulates the pharmacodynamic effect of high-dose methotrexate in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma: \u2018folate overrescue\u2019 concept revisited. Clin Chem 2006; 52: 692\u2013700.","journal-title":"Clin Chem"},{"key":"BFtpj201463_CR52","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/pbc.24770","volume":"61","author":"IJ Cohen","year":"2014","unstructured":"Cohen IJ, Wolff JE . How long can folinic acid rescue be delayed after high-dose methotrexate without toxicity? Pediatr Blood Cancer 2014; 61: 7\u201310.","journal-title":"Pediatr Blood Cancer"},{"key":"BFtpj201463_CR53","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.tips.2008.01.006","volume":"29","author":"FG Russel","year":"2008","unstructured":"Russel FG, Koenderink JB, Masereeuw R . Multidrug resistance protein 4 (MRP4\/ABCC4): a versatile efflux transporter for drugs and signalling molecules. Trends Pharmacol Sci 2008; 29: 200\u2013207.","journal-title":"Trends Pharmacol Sci"},{"key":"BFtpj201463_CR54","doi-asserted-by":"publisher","first-page":"R130","DOI":"10.1186\/gb-2009-10-11-r130","volume":"10","author":"C Wu","year":"2009","unstructured":"Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S et al. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 2009; 10: R130.","journal-title":"Genome Biol"},{"key":"BFtpj201463_CR55","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/bioinformatics\/btq330","volume":"26","author":"W McLaren","year":"2010","unstructured":"McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F . Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 2010; 26: 2069\u20132070.","journal-title":"Bioinformatics"},{"key":"BFtpj201463_CR56","first-page":"1575","volume":"38","author":"J Samuelsson","year":"2011","unstructured":"Samuelsson J, Alonso S, Ruiz-Larroya T, Cheung TH, Wong YF, Perucho M . Frequent somatic demethylation of RAPGEF1\/C3G intronic sequences in gastrointestinal and gynecological cancer. Int J Oncol 2011; 38: 1575\u20131577.","journal-title":"Int J Oncol"}],"container-title":["The Pharmacogenomics Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/tpj201463.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tpj201463","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tpj201463.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T12:34:02Z","timestamp":1717504442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/tpj201463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,4]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["BFtpj201463"],"URL":"https:\/\/doi.org\/10.1038\/tpj.2014.63","relation":{},"ISSN":["1470-269X","1473-1150"],"issn-type":[{"value":"1470-269X","type":"print"},{"value":"1473-1150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,4]]},"assertion":[{"value":"6 May 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2014","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2014","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}