Fig. 6: Proposed model showing the mechanism of combined FLT3 and Notch inhibition. | Signal Transduction and Targeted Therapy

Fig. 6: Proposed model showing the mechanism of combined FLT3 and Notch inhibition.

From: Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD+ acute myeloid leukemia

Fig. 6

a At baseline, FLT3-ITD signaling results in high ERK activity and, therefore, high expression of survival and cell proliferation genes. b Following treatment with FLT3-TKIs, ERK activity mediated by FLT3-ITD signaling is inhibited, while Notch signaling and CXCR3 expression are upregulated, resulting in alternative ERK activation. c GSI addition abrogates the rebound by blocking Notch signaling and decreasing CXCR3 activity, thus resulting in extreme repression of ERK activity and a synergistic antitumor effect.

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