The Aurora kinase/β-catenin axis contributes to dexamethasone resistance in leukemia

Abstract Glucocorticoids, such as dexamethasone and prednisolone, are widely used in cancer treatment. Different hematological malignancies respond differently to this treatment which, could be expected, correlates with outcome. In study, we have a glucocorticoid-induced gene signature develop deep learning model that can predict sensitivity. By combining expression data from cell lines patients acute lymphoblastic leukemia, observed the is useful for classification of patients. Predicted samples been detect deregulated pathways lead resistance. Gene set enrichment analysis, peptide substrate-based kinase profiling assay, western blot analysis identified Aurora kinase, S6K, p38, β-catenin key signaling proteins involved Deep learning-enabled drug synergy prediction followed by vitro inhibitors against JAK, mTOR displayed dexamethasone. Combining pathway enrichment, regulation, inhibition data, propose or its several direct indirect downstream effectors mTOR, JAK may stabilization through phosphorylation-dependent inactivation GSK-3β. Collectively, our suggest activation kinase/β-catenin axis during contribute survival which possibly maintained who resistant