{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:48:47Z","timestamp":1781920127357,"version":"3.54.5"},"reference-count":173,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Pharmacogenomics (PGx) has emerged as a key strategy to predict and prevent drug hypersensitivity reactions and treatment-related toxicities, thereby improving therapeutic adherence and survival in cancer care. Despite major advances in survival outcomes for pediatric B-Acute Lymphoblastic Leukemia (B-ALL), treatment-related toxicities remain a significant clinical challenge. Notably, treatment de-escalation strategies for low-risk leukemia are currently being explored in several clinical trials to reduce therapy-related toxicities. This review focuses on the mechanisms of drug-induced toxicity and their association with pharmacogenetic determinants in B-ALL therapy. Among the pharmacogenetic factors influencing toxicity of commonly used B-ALL treatments, variants in the\n                    <jats:italic>TPMT<\/jats:italic>\n                    and\n                    <jats:italic>NUDT15<\/jats:italic>\n                    genes, both involved in the metabolism of 6-mercaptopurine, represent the most robust and clinically validated predictors. Emerging evidence also links additional genetic variants to toxicities associated with other key agents used in ALL treatment regimens, including variants in\n                    <jats:italic>SLCO1B1<\/jats:italic>\n                    associated with methotrexate-related gastrointestinal toxicity and variants in\n                    <jats:italic>CEP72<\/jats:italic>\n                    associated with vincristine-induced neuropathy. The integration of pharmacogenomic biomarkers into clinical protocols, enabling genotype-guided dose adjustment, may represent a valuable strategy to avoid toxicity and improve overall cancer outcomes. However, further studies and innovative approaches are required to validate emerging biomarkers and facilitate their translation into routine clinical practice.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1806729","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:44:29Z","timestamp":1779169469000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Meriem","family":"Lameri","sequence":"first","affiliation":[{"name":"Centre National de Transfusion Sanguine","place":["Tunis, Tunisia"]},{"name":"Pharmaceutical Sciences A Department, Clinical Biology A Department, Universite de Monastir, Faculte de Pharmacie de Monastir","place":["Monastir, 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Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosr","family":"Ben Abdennebi","sequence":"additional","affiliation":[{"name":"Pediatric Clinical Hematology, Hopital Aziza Othmana","place":["Tunis, Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Razgallah","family":"Khrouf","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences A Department, Clinical Biology A Department, Universite de Monastir, Faculte de Pharmacie de Monastir","place":["Monastir, Tunisia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorra","family":"Amor","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences A Department, Clinical Biology A Department, Universite de Monastir, Faculte de Pharmacie de Monastir","place":["Monastir, Tunisia"]},{"name":"Department of Biochemistry, LR12SP11, Hopital Sahloul","place":["Sousse, 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