Proteome-based identification and validation of NXPE3 in childhood acute lymphoblastic leukaemia

Background: Childhood acute lymphoblastic leukaemia (cALL) tends to metastasize to central nervous system. Treatment with antileukemic agents against CNS leukaemia is an essential component for cure in ALL. Hence, it is essential to identify biomarkers for CNS infiltration. Proteomics, supported by mass spectrometry, is the platform for exploring biomarkers in various biological samples, contributing to translational research. Objectives: This study aimed to identify the plasma proteome profile of children across different risk groups of cALL. Neurexophilin and PC-esterase family, member 3 (NXPE3), was validated. The protein-protein interactions (PPI) of NXPE3 were evaluated with bioinformatics analyses. Methods: Plasma samples from 15 patients with B-ALL standard risk (SR), B-ALL high risk (HR) and T-ALL high risk (HR), were analysed using LC-MS/MS. NXPE3 protein was validated in all risk groups using ELISA. To compare the NXPE3 values across groups, the Kruskal-Wallis test was applied. A p-value < 0.05 was considered significant. STRING database was used for PPI. Results: LC MS/MS analysis showed upregulation of NXPE3 in B-ALL SR. Upon ELISA validation, a high plasma concentration of NXPE3 was observed in B-ALL SR, 4.37±1.84 ng/ml (95% CI 3.31, 5.44), consistent with LC MS/MS findings. A lower concentration of NXPE3 was observed in B-ALL HR 2.68±1.34 ng/ml and T-ALL HR 2.38±0.92ng/ml. The findings were statistically significant. The PPI of NXPE3 highlighted its involvement in multiple processes, including gene expression, cytoskeletal organisation and neuronal function. Conclusion: This is the first report of NXPE3 in cALL. NXPE3 was identified as a potential biomarker for assessing CNS infiltration in cALL. Further studies are recommended to explore its role in leukemogenesis.