FLT3-ITD scaffolds PKCι-STAT1 to drive noncanonical S727 phosphorylation and CD276-driven CD8+ T-cell exhaustion in AML

The authors investigate the kinase-independent mechanisms of immune evasion associated with the FLT3-ITD mutation in acute myeloid leukemia (AML), particularly focusing on the role of CD8+ T cell exhaustion. They identify a novel signaling axis involving FLT3-ITD, PKCι, and STAT1 that leads to phosphorylation of STAT1 at serine 727, driving the expression of CD276, which in turn contributes to T cell dysfunction. The study suggests that targeting both FLT3 and CD276 may enhance therapeutic outcomes in FLT3-ITD AML by restoring T cell function.