This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.
Moreover, the JAK1/2 inhibitor ruxolitinib restored sensitivity to the BCL2 inhibitor venetoclax in AML patient cells ex vivo in different model systems and in vivo in an AML xenograft mouse model.
Therefore, our novel findings indicated that CUEDC2 interacted with SOCS1 to suppress SOCS1's ubiquitin-mediated degradation, JAK1-STAT3 pathway activation and leukaemogenesis of AML.