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

Experimental Hematology
Ikuko OmoriKoiti Inokuchi

Abstract

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 KITD816V, TF-1 KITN822K). 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 KITD816Vthan in TF-1 KITN822K(p = 0.022). When Ara-C was added in the absence of growth factor, Annexin V assay revealed that TF-1 KITD816Vwas associated with a significantly lower proportion of apoptotic cells than TF-1 KITN822K(p < 0.001). Regarding signal transduction pathways, both KIT D816V and KIT N822K underwent autophosphorylation in the absence of growth factor. This was followed in KIT D816V by downstream activation of the SRC family kinase pathway in addition to the Janus kinase/signal transducers and activators of transcri...Continue Reading

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Citations

Dec 20, 2018·Stem Cells·Federica TodaroSusanna Dolci
Feb 19, 2019·Expert Opinion on Investigational Drugs·Joseph Cioccio, David Claxton
Jul 28, 2020·Cancers·Edwige VoissetPaulo de Sepulveda
Jun 12, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Katherine TarlockJessica A Pollard

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