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. 2025 May 11;17(10):1623.
doi: 10.3390/cancers17101623.

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

Karine Pereira de Andrade  1   2 , Gustavo Lovatto Michaelsen  3 , Lívia Fratini Dutra  1 , Rebeca Ferreira Marques  1   4 , Daniela Elaine Roth Benincasa  5 , Júlia Plentz Portich  1   6 , Jiseh Fagundes Loss  4 , Lauro José Gregianin  4   7 , André Tesainer Brunetto  3   7 , Marialva Sinigaglia  3   7 , Rafael Roesler  1   7   8 , Mariane da Cunha Jaeger  1   3   7 , Marcelo Land  7   9   10 , Caroline Brunetto de Farias  1   2   3   7   10
Affiliations

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

Karine Pereira de Andrade et al. Cancers (Basel). .

Abstract

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.

Keywords: ALL; BDNF; childhood leukemia; neurotrophins; prognosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Pro-BDNF levels in healthy individuals and children at ALL timepoints (median IQR 75–25% within the box limits), with statistical significance from the Mann–Whitney test between two groups indicated as △ for p < 0.001 and as □ for p < 0.05. After FDR correction, all comparisons remained significant except for the comparison between healthy individuals and those diagnosed with relapse, likely due to the small sample size.
Figure 2
Figure 2
BDNF levels in healthy individuals and children at ALL timepoints (median IQR 75–25% 75–25% within the box limits), with statistical significance from the Mann–Whitney test between two groups indicated as △ for p < 0.001 and as □ for p < 0.05. After FDR correction, all comparisons remained significant except comparison between disease stages maintenance and relapse diagnosis, likely due to small sample size.
Figure 3
Figure 3
NGF levels in healthy individuals and children ALL timepoints (median IQR 75–25% 75–25% within the box limits), with statistical significance from the Mann–Whitney test between two groups indicated as △ for p < 0.001 and as □ for p < 0.05. After applying FDR correction for false positives, all previously significant results remained statistically significant.
Figure 4
Figure 4
NT levels in ALL patients during clinical evolution. There is a strong positive correlation between BDNF and pro-BDNF levels (Pearson’s r = 0.87). BDNF and pro-BDNF protein levels are lower in diagnosis and relapse when compared to the treatment maintenance and disease remission (follow-up).
Figure 5
Figure 5
Kaplan–Meier estimate of overall survival (OS) of children and adolescents with ALL stratified by pro-BDNF high and low levels (p < 0.05).
See this image and copyright information in PMC

References

    1. Hillis J., O’Dwyer M., Gorman A.M. Neurotrophins and B-cell malignancies. Cell. Mol. Life Sci. 2015;73:41–56. doi: 10.1007/s00018-015-2046-4. - DOI - PMC - PubMed
    1. Vega J.A., García-Suárez O., Hannestad J., Pérez-Pérez M., Germanà A. Neurotrophins and the immune system. J. Anat. 2003;203:1–19. doi: 10.1046/j.1469-7580.2003.00203.x. - DOI - PMC - PubMed
    1. Costa R.O., Perestrelo T., Almeida R.D. PROneurotrophins and CONSequences. Mol. Neurobiol. 2017;55:2934–2951. doi: 10.1007/s12035-017-0505-7. - DOI - PubMed
    1. Gray K., Ellis V. Activation of pro-BDNF by the pericellular serine protease plasmin. FEBS Lett. 2008;582:907–910. doi: 10.1016/j.febslet.2008.02.026. - DOI - PubMed
    1. Lee R., Kermani P., Teng K.K., Hempstead B.L. Regulation of cell survival by secreted proneurotrophins. Science. 2001;294:1945–1948. doi: 10.1126/science.1065057. - DOI - PubMed

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