WNT6 affects the prognosis of pediatric acute myeloid leukemia through regulation of Wnt signaling pathway activity

Abstract

Abstract Purpose Pediatric acute myeloid leukemia (AML) is associated with a dismal prognosis, underscoring the urgent need to identify potential biomarkers that can aid in the management of pediatric AML patients. Methods The adult AML dataset GSE201492 was partitioned into distinct prognostic groups following the identification of key genes through the screening of differentially expressed genes, enrichment analysis, and protein-protein interaction (PPI) analysis. Subsequently, these key genes were validated in the pediatric AML dataset obtained from the TARGET database, as well as in the data of pediatric AML patients diagnosed at the First Affiliated Hospital of Zhengzhou University. Finally, the association between WNT6 and the Wnt signaling pathway was investigated using the AML drug resistance dataset (GSE214158) and the WNT6 knockout dataset (GSE160039). Results Through the analysis of different prognostic groups in adult AML, researchers identified five key genes. The results from the TARGET database and clinical samples showed that pediatric AML patients with low expression of the gene WNT6 had better overall survival. In a dataset where WNT6 was knocked down, there was a significant decrease in the Wnt signaling pathway score. In another dataset about AML resistance, there was a statistically significant difference in Wnt signaling pathway scores, with the UTX knockout group having lower scores. Conclusion The upregulation of WNT6 has been recognized as a predictive factor for adverse prognoses in pediatric AML. Additionally, it contributes to the emergence of drug resistance in AML by modulating the functionality of the Wnt signaling pathway.