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Título

Neurotrophins as potential biomarkers for poor prognosis in childhood acute lymphoid leukemia

Resumo

BACKGROUND: Neurotrophins (NTs) are growth factors involved in development and survival of several types of cells. Their mechanism is extensively related to cancer, however in Acute Lymphoid Leukemia (ALL), its role remains unclear. OBJECTIVE: The study aims to investigate the NT’s role in childhood ALL, assessing gene expression of the main genes of this pathway and measuring its protein levels. METHODS: NT’s genes expressions in pediatric samples collected in a public genomic data repository were performed in R software. ALL pediatric patient’s samples in different moments of disease were collected from 2011 to 2021 in Brazil’s health institutions. The protein levels were measured by ELISA test according to manufacturer indication. Overall survival was evaluated by Kaplar-Meier curve, adopting NT level median as cut number. RESULTS: NGF and sortilin were found overexpressed in health samples when compared with tumor samples, while BDNF and P75 NTR were found overexpressed in T-cell tumor and B-cell tumor samples, respectively. Enzyme convertases from pro-NTs to NTs were overexpressed in disease samples. Protein levels were lower in samples at diagnosis when compared to healthy individuals. A correlation between pro-BDNF and BDNF levels during disease was found. Patients with lower pro-BDNF at diagnosis also presented a worse overall survival than patients with higher pro-BDNF levels at diagnosis (pLogrank=0.049). CONCLUSIONS: NTs are altered in tumor-microenvironment in childhood ALL. Further studies are required to understand their complete role in this context.