{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:14:58Z","timestamp":1760058898292,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children\u2019s Cancer Institute (ICI)"},{"name":"Research Incentive Fund of Clinical Hospital (FIPE\/HCPA)"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology (INCT BioOncoPed)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Neurotrophins (NTs) are pivotal growth factors in cellular development and survival. Their precise implications in Acute Lymphoblastic Leukemia (ALL) remain unclear. Methods: Pediatric ALL samples (2011\u20132021) were analyzed from a Southern Brazil cohort. Neurotrophin levels were quantified via ELISA, with survival analysis using Kaplan\u2013Meier curves. Gene expression data were sourced from public genomic repositories and analyzed with R software version 4.0.5. Results: At diagnosis, pro-BDNF, BDNF, and NGF levels were significantly lower than in healthy controls. Reduced pro-BDNF correlated with unfavorable outcomes. NGF and sortilin were highly expressed in healthy samples, while BDNF and p75NTR were predominant in T-ALL and B-ALL, respectively. Conclusions: Neurotrophins show significant alterations in the tumor microenvironment of pediatric ALL. Further studies are needed to elucidate their precise role and prognostic potential.<\/jats:p>","DOI":"10.3390\/cancers17101623","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T04:21:23Z","timestamp":1747023683000},"page":"1623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurotrophins as Potential Biomarkers for Active Disease and Poor Outcome in Pediatric Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"17","author":[{"given":"Karine Pereira","family":"de Andrade","sequence":"first","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"Postgraduate Program in Pharmacology and Therapeutics, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Lovatto","family":"Michaelsen","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1592-0830","authenticated-orcid":false,"given":"L\u00edvia Fratini","family":"Dutra","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca Ferreira","family":"Marques","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"Pediatric Oncology Service, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Elaine Roth","family":"Benincasa","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Service, Concei\u00e7\u00e3o Children Hospital, Porto Alegre 91350-250, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4633-2903","authenticated-orcid":false,"given":"J\u00falia Plentz","family":"Portich","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"Hematology and Hemotherapy Service, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiseh Fagundes","family":"Loss","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Service, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-7858","authenticated-orcid":false,"given":"Lauro Jos\u00e9","family":"Gregianin","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Service, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7958-1279","authenticated-orcid":false,"given":"Andr\u00e9 Tesainer","family":"Brunetto","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-6860","authenticated-orcid":false,"given":"Marialva","family":"Sinigaglia","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-2261","authenticated-orcid":false,"given":"Rafael","family":"Roesler","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"},{"name":"Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariane","family":"da Cunha Jaeger","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"Children\u2019s Cancer Institute, Porto Alegre 90620-110, RS, Brazil"},{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Land","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology in Childhood Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90050-170, RS, Brazil"},{"name":"Department of Pediatrics, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-912, RJ, Brazil"},{"name":"Martag\u00e3o Gesteira Childcare and Pediatrics Institute, Federal University of Rio de Janeiro, Rio de Janeiro 21941-912, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline Brunetto","family":"de Farias","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre\u2019s Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"},{"name":"Postgraduate Program 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