{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:59:10Z","timestamp":1768409950190,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"American University of Beirut Medical Practice Plan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Interindividual variability in thiopurine\u2010related toxicity could not be completely explained by thiopurine S\u2010methyltransferase (TPMT) polymorphisms, as a number of patients who are homozygous wild type or normal for TPMT still develop toxicity that necessitates 6\u2010mercaptopurine (MP) dose reduction or protocol interruption. Recently, few studies reported on an inherited nucleoside diphosphate\u2010linked moiety X motif 15 (NUDT15) c.415C&gt;T low\u2010function variant that is associated with decreased thiopurine metabolism and leukopenia in childhood acute lymphoblastic leukemia (ALL) and other diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>The aim of this study is to measure the frequency of TPMT and NUDT15 polymorphisms and assess whether they are predictors of MP intolerance in children treated for ALL. One hundred thirty\u2010seven patients with ALL of whom 121 were Lebanese were evaluated. MP dose intensity was calculated as the ratio of the tolerated MP dose to planned dose during continuation phase to maintain an absolute neutrophil count (ANC) dose above 300 per \u03bcl.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One patient was NUDT15 heterozygous TC and tolerated only 33.33% of the planned MP dose, which was statistically significantly different from the median\u2010tolerated MP dose intensity of the rest of the cohort (76.00%). Three patients had the TPMT*3A haplotype and tolerated 40.00\u201366.66% of the planned MP dose, which was also statistically significantly different from the rest of the cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first report on the association of TPMT and NUDT15 polymorphisms with MP dose intolerance in Arab patients with ALL. Genotyping for additional polymorphisms may be warranted for potential gene\/allele\u2010dose effect.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26189","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T17:25:43Z","timestamp":1472750743000},"page":"146-150","source":"Crossref","is-referenced-by-count":42,"title":["NUDT15 and TPMT genetic polymorphisms are related to 6\u2010mercaptopurine intolerance in children treated for acute lymphoblastic leukemia at the Children's Cancer Center of Lebanon"],"prefix":"10.1002","volume":"64","author":[{"given":"Nathalie K.","family":"Zgheib","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology American University of Beirut, Faculty of Medicine  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Akika","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology American University of Beirut, Faculty of Medicine  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rami","family":"Mahfouz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol Al","family":"Aridi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled M.","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raya","family":"Saab","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel R.","family":"Abboud","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidale","family":"Tarek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"El Solh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar A.","family":"Muwakkit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Children's Cancer Institute, American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2008.09.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181868570"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31391"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.10139"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23222"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000069"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328334338f"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.4671"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3508"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.134775"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13518"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3060"},{"key":"e_1_2_8_15_1","first-page":"1","article-title":"NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia","author":"Liang DC","year":"2015","journal-title":"Pharmacogenomics J"},{"key":"e_1_2_8_16_1","first-page":"1","article-title":"Genotyping NUDT15 can predict the dose reduction of 6\u2010MP for children with acute lymphoblastic leukemia especially at a preschool age","author":"Suzuki H","year":"2016","journal-title":"J Hum Genet"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.12809\/hkmj154783"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000564"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1142-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.43"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.363010"},{"key":"e_1_2_8_22_1","unstructured":"U.S. Department of Health and Human Services. National Institutes of Health. National Cancer Institute. Cancer Therapy Evaluation Program. Bethesda MD. Common Toxicity Criteria Manual; 1999.http:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/docs\/ctcmanual_v4_10-4-99.pdf"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.26189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.26189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T20:53:54Z","timestamp":1695761634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.26189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,31]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1002\/pbc.26189"],"URL":"https:\/\/doi.org\/10.1002\/pbc.26189","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,31]]}}}