# Neurotrophins as Potential Biomarkers for Active Disease and Poor Outcome in Pediatric Acute Lymphoblastic Leukemia

**Authors:** Karine Pereira de Andrade, Gustavo Lovatto Michaelsen, Lívia Fratini Dutra, Rebeca Ferreira Marques, Daniela Elaine Roth Benincasa, Júlia Plentz Portich, Jiseh Fagundes Loss, Lauro José Gregianin, André Tesainer Brunetto, Marialva Sinigaglia, Rafael Roesler, Mariane da Cunha Jaeger, Marcelo Land, Caroline Brunetto de Farias

PMC · DOI: 10.3390/cancers17101623 · Cancers · 2025-05-11

## TL;DR

This study shows that lower levels of neurotrophins in children with leukemia are linked to active disease and worse outcomes, suggesting they could be useful biomarkers.

## Contribution

The study identifies specific neurotrophin patterns in pediatric ALL and links them to disease activity and prognosis.

## Key findings

- Lower pro-BDNF, BDNF, and NGF levels at diagnosis correlate with active disease and poor outcomes in pediatric ALL.
- NGF and sortilin are highly expressed in healthy samples, while BDNF and p75NTR are predominant in T-ALL and B-ALL, respectively.
- Neurotrophins show significant alterations in the tumor microenvironment of pediatric ALL.

## Abstract

Neurotrophins are essential growth factors involved in cellular development and survival. Their role in Acute Lymphoblastic Leukemia (ALL) remains to be fully elucidated. This study evaluates neurotrophin levels in pediatric ALL patients and investigates their relationship with disease phases and outcomes. Our findings suggest that decreased neurotrophin levels at diagnosis correlate with active disease and worse outcomes, indicating their potential as biomarkers when assessing ALL in children.

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 (2011–2021) were analyzed from a Southern Brazil cohort. Neurotrophin levels were quantified via ELISA, with survival analysis using Kaplan–Meier 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.

## Linked entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627], NGF (nerve growth factor) [NCBI Gene 4803], NGFR (nerve growth factor receptor) [NCBI Gene 4804], sort1.S (sortilin 1 S homeolog) [NCBI Gene 100158281]
- **Diseases:** Acute Lymphoblastic Leukemia (MONDO:0004967), ALL (MONDO:0004967), T-ALL (MONDO:0004963), B-ALL (MONDO:0020511)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, PSIP1 (PC4 and SRSF1 interacting protein 1) [NCBI Gene 11168] {aka DFS70, LEDGF, PAIP, PSIP2, p52, p75}, SORT1 (sortilin 1) [NCBI Gene 6272] {aka Gp95, LDLCQ6, NT3, NTR3}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, NTSR1 (neurotensin receptor 1) [NCBI Gene 4923] {aka NTR}
- **Diseases:** ALL (MESH:D054198), tumor (MESH:D009369)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12110685/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12110685/full.md

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Source: https://tomesphere.com/paper/PMC12110685