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It is of particular interest to identify drugs to overcome these resistances. In this study, we found that <jats:styled-content style=\"fixed-case\">PRPS<\/jats:styled-content>1 mutant <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells specifically showed more chemosensitivity to 5\u2010Fluorouracil (5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content>) than control cells, attributed to increased apoptosis of <jats:styled-content style=\"fixed-case\">PRPS<\/jats:styled-content>1 mutant cells by 5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content>. Mechanistically, <jats:styled-content style=\"fixed-case\">PRPS<\/jats:styled-content>1 mutants increase the level of intracellular phosphoribosyl pyrophosphate (<jats:styled-content style=\"fixed-case\">PRPP<\/jats:styled-content>), which causes the apt conversion of 5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">FUMP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">FUTP<\/jats:styled-content> in Reh cells, to promote 5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage and apoptosis. Our study not only provides mechanistic rationale for re\u2010targeting drug resistant cells in <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>, but also implicates that <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> patients who harbor relapse\u2010specific mutations of <jats:styled-content style=\"fixed-case\">PRPS<\/jats:styled-content>1 might benefit from 5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content>\u2010based chemotherapy in clinical settings.<\/jats:p>","DOI":"10.1111\/jcmm.13907","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T06:28:28Z","timestamp":1537943308000},"page":"6202-6212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Increase of <scp>PRPP<\/scp> enhances chemosensitivity of <scp>PRPS<\/scp>1 mutant acute lymphoblastic leukemia cells to 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