Synergistic effect of FMS-like tyrosine kinase-3 (FLT3) inhibitors combined with a CDK7 inhibitor in FLT3-ITD-mutated acute myeloid leukemia

This is the authors' abstract. We don't add key points for this paper.

Acute myeloid leukemia (AML) is frequently associated with FLT3 mutations, which are present in approximately 30% of cases. These mutations are associated with a poor prognosis, frequent relapses, and reduced overall survival [ 1 , 2 ]. FLT3 mutations lead to constitutive activation of the tyrosine kinase and subsequent downstream proliferation cascades, such as those regulated by STAT5, resulting in uncontrolled proliferation of leukemic cells [ 3 , 4 ]. Small molecule tyrosine kinase inhibitors (TKIs) that specifically target FLT3 have improved survival rates in patients with FLT3 -mutated AML [ 5 ]. Although these agents have demonstrated significantly better survival outcomes compared to patients treated with placebos or salvage chemotherapy, a substantial proportion of patients still experience disease relapse, primarily due to the development of primary and secondary resistance to FLT3-TKIs [ 6 , 7 , 8 , 9 ].