D816V mutation in the KIT gene activation loop has greater cell-proliferative and anti-apoptotic ability than N822K mutation in core-binding factor acute myeloid leukemia

In core-binding factor acute myeloid leukemia (CBF-AML), there have been conflicting reports regarding the status as an unfavorable prognostic factor of mutation in the KIT gene, the significance of which remains unclear. We previously reported that prognoses differ between the KIT D816V and N822K mutations. In the present study, we compared in vitro the cell-proliferative and anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into the interleukin-3–dependent cell line TF-1 (TF-1 KIT D816V , TF-1 KIT N822K ). When these KIT mutations were transduced into TF-1 cells, the cells acquired a proliferative ability independent of growth factor, which was significantly higher in TF-1 KIT D816V than in TF-1 KIT N822K ( p  = 0.022). When Ara-C was added in the absence of growth factor, Annexin V assay revealed that TF-1 KIT D816V was associated with a significantly lower proportion of apoptotic cells than TF-1 KIT N822K ( p