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Currently, testing for NUDT15 deficiency is based on the genotyping of the most frequent and clinically characterized no\u2010function variants, that is, *\n                    <jats:italic>2<\/jats:italic>\n                    , *\n                    <jats:italic>3<\/jats:italic>\n                    and *\n                    <jats:italic>9<\/jats:italic>\n                    . The Hispanic\/Latino\u2010predominant variant\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>4<\/jats:italic>\n                    (p.R139H) is classified as \u201cuncertain function\u201d by the Clinical Pharmacogenetics Implementation Consortium, because of insufficient data to ascertain its clinical actionability. In this study, we evaluated the association of\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>4<\/jats:italic>\n                    with mercaptopurine (6\u2010MP) tolerance in a retrospective cohort of 1,399 patients with acute lymphoblastic leukemia (ALL) of diverse ancestries. All patients were wildtype for thiopurine methyltransferase gene. Patients were treated with 6\u2010MP in the context of ALL frontline clinical trials. The tolerated dose of 6\u2010MP was used to assess drug toxicity during the maintenance phase of ALL therapy. Patients with\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>1<\/jats:italic>\n                    \/*\n                    <jats:italic>4<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916, all of whom self\u2010identified as Hispanic\/Latino) tolerated a significantly lower dose of 6\u2010MP than did those with\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>1<\/jats:italic>\n                    \/*\n                    <jats:italic>1<\/jats:italic>\n                    : median [interquartile range] of 39.0 [21.2\u201352.8] mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , vs. 62.2 [47.9\u201371.6] mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    value &lt;\u20090.001. No patient homozygous for *\n                    <jats:italic>4<\/jats:italic>\n                    was detected. In a separate retrospective validation study, six patients were identified as having\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>1<\/jats:italic>\n                    \/*\n                    <jats:italic>4<\/jats:italic>\n                    by routine clinical pharmacogenetics testing and tolerated a 6\u2010MP median dose of 38.7\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    (IQR, 33.7\u201354.0), confirming the need for dose reduction attributed to the\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>4<\/jats:italic>\n                    variant. These results point to the need to include\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *\n                    <jats:italic>4<\/jats:italic>\n                    in pharmacogenetics\u2010guided thiopurine dosing algorithms.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3501","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T07:13:39Z","timestamp":1734419619000},"page":"724-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Actionability of the\n                    <i>NUDT15<\/i>\n                    *\n                    <i>4<\/i>\n                    (p.\n                    <scp>R139H<\/scp>\n                    ) Allele and Its Association With Hispanic Ethnicity"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-3136","authenticated-orcid":false,"given":"Maud","family":"Maillard","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7190-1231","authenticated-orcid":false,"given":"Jenny Q.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Personalized Care Program Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-5649","authenticated-orcid":false,"given":"Wenjian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-0711","authenticated-orcid":false,"given":"Keito","family":"Hoshitsuki","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-9591","authenticated-orcid":false,"given":"Mary V.","family":"Relling","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-3793","authenticated-orcid":false,"given":"Kelly E.","family":"Caudle","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences St. Jude Children's Research Hospital  Memphis Tennessee 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