{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:19Z","timestamp":1785416479305,"version":"3.56.0"},"reference-count":81,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00278088"],"award-info":[{"award-number":["RS-2023-00278088"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2023-00278088"],"award-info":[{"award-number":["RS-2023-00278088"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurological complications, particularly seizures, represent a significant and often under-recognized clinical challenge in pediatric hematologic malignancies. Distinguishing CNS leukemia-associated epilepsy from chemotherapy-induced neurotoxicity is critical for optimizing therapy but remains difficult due to overlapping clinical presentations. This review highlights the distinct molecular mechanisms underlying these two entities. CNS leukemia-associated seizures are primarily driven by blood\u2013brain barrier (BBB) disruption following leukemic infiltration, which triggers a neuroinflammatory cascade involving pro-inflammatory cytokines such as IL-6 and TNF-\u03b1, and impairs glutamate homeostasis. In contrast, chemotherapy-induced seizures, particularly those associated with high-dose methotrexate, arise from disrupted folate metabolism, intracellular oxidative stress, and subsequent N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. We provide a comparative analysis of these pathways, integrating current evidence on pharmacogenomic susceptibility\u2014including polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and drug transporter genes\u2014as well as epigenetic factors. By synthesizing these molecular insights, we propose a mechanistic framework for precise clinical differentiation, which may inform biomarker-driven diagnostic approaches and targeted neuroprotective strategies in this vulnerable population.<\/jats:p>","DOI":"10.3390\/ijms27073307","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:09:00Z","timestamp":1775549340000},"page":"3307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Mechanistic Divergence of Seizures in Pediatric Acute Lymphoblastic Leukemia: CNS Infiltration Versus Chemotherapy-Induced Neurotoxicity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-9397","authenticated-orcid":false,"given":"Jin","family":"Joo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and pain Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Sub","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9634-5120","authenticated-orcid":false,"given":"Hyun Jung","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and pain Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100593","DOI":"10.1016\/j.lansea.2025.100593","article-title":"Risk stratified treatment for childhood acute lymphoblastic leukaemia: A multicentre observational study from India","volume":"37","author":"Gogoi","year":"2025","journal-title":"Lancet Reg. 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