Noncanonical FLT3-ITD Signaling Drives Immune Evasion via PKCι-STAT1–Mediated CD8+ T-Cell Exhaustion in Acute Myeloid Leukemia

MedXY Editorial Team•Jul 15, 2026•Hematology-Oncology

FLT3-ITD mutations in acute myeloid leukemia (AML) promote CD8+ T-cell exhaustion through a kinase-independent scaffolding mechanism.
FLT3-ITD scaffolds protein kinase C iota (PKCι) and STAT1 to drive noncanonical phosphorylation of STAT1 at serine 727, enhancing CD276 expression.
CD276 upregulation induces CD8+ T-cell dysfunction characterized by reduced cytotoxicity, proliferation, and interferon-γ production, along with increased inhibitory checkpoint expression.
Combined targeting of FLT3 with quizartinib and CD276 enhances antileukemic efficacy and restores T-cell functionality in patient-derived xenograft models more effectively than FLT3 inhibition alone.

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This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

FLT3-ITD mutations in acute myeloid leukemia (AML) promote CD8+ T-cell exhaustion through a kinase-independent scaffolding mechanism.
FLT3-ITD scaffolds protein kinase C iota (PKCι) and STAT1 to drive noncanonical phosphorylation of STAT1 at serine 727, enhancing CD276 expression.
CD276 upregulation induces CD8+ T-cell dysfunction characterized by reduced cytotoxicity, proliferation, and interferon-γ production, along with increased inhibitory checkpoint expression.
Combined targeting of FLT3 with quizartinib and CD276 enhances antileukemic efficacy and restores T-cell functionality in patient-derived xenograft models more effectively than FLT3 inhibition alone.