{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:23:00Z","timestamp":1789010580436,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Chinese children are more susceptible to the development of thiopurine\u2010induced leukopenia compared with Caucasian populations. The aim of our study was to establish a 6\u2010mercaptopurine (6\u2010MP) dose\u2013concentration\u2013response relationship through exploration of pharmacogenetic factors involved in the thiopurine\u2010induced toxicities in Chinese paediatric patients afflicted by acute lymphoblastic leukaemia (ALL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples were obtained from ALL children treated with 6\u2010MP. We determined the metabolite steady\u2010state concentrations of 6\u2010MP in red blood cells (RBCs) by using high\u2010performance liquid chromatography. Pharmacogenetic analysis was carried out on patients' genomic DNA using the MassArray genotyping platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty children afflicted by ALL who received 6\u2010MP treatment were enrolled in this study. The median concentration of 6\u2010thioguanine in patients afflicted by leukopenia was 235.83 pmol\/8 \u00d7 10<jats:sup>8<\/jats:sup> RBCs, which was significantly higher than for patients unafflicted by leukopenia (178.90 pmol\/8 \u00d7 10<jats:sup>8<\/jats:sup> RBCs; <jats:italic>P<\/jats:italic> = 0.029). We determined the population special target 6\u2010thioguanine threshold to have equalled 197.50 pmol\/8 \u00d7 10<jats:sup>8<\/jats:sup> RBCs to predict leukopenia risk in Chinese paediatric patients afflicted by ALL. Among 36 candidate single nucleotide polymorphisms, our results indicated that <jats:italic>NUDT15<\/jats:italic> (rs116855232) and <jats:italic>IMPDH1<\/jats:italic> (rs2278293) were correlated with a 5.50\u2010fold and 5.80\u2010fold higher risk of leukopenia, respectively. <jats:italic>MTHFR<\/jats:italic> rs1801133 variants were found to have had a 4.46\u2010fold significantly higher risk of hepatotoxicity <jats:italic>vs<\/jats:italic> wild\u2010type genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings support the idea that predetermination of genotypes and monitoring of thiopurine metabolism for Chinese paediatric patients afflicted by ALL is necessary to effectively predict the efficacy of treatments and to minimize the adverse effects of 6\u2010MP maintenance therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14258","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T07:41:46Z","timestamp":1582184506000},"page":"1519-1527","source":"Crossref","is-referenced-by-count":15,"title":["Precision therapy of 6\u2010mercaptopurine in Chinese children with acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"86","author":[{"given":"Yue","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Sciences Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology\u2010Oncology Children's Hospital of Hebei Province affiliated to Hebei Medical University  Shijiazhuang 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