Combinatorial inhibition of Notch and FLT3 exerts synergistic cytotoxic effects in FLT3/ITD+ acute myeloid leukemia

ABSTRACT: we observed synergistic cytotoxic effects, preferentially reducing cell proliferation and inducing apoptosis in FLT3/ITD+ AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in a FLT3/ITD+ patient derived xenograft (PDX) AML model. Mechanistically, decreased expression of CXCR3 that lead to down-regulated ERK signaling was partially responsible for the observed synergy. Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD+ AML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126933 | GEO | 2019/02/23

REPOSITORIES: GEO