Fig. 7: Mechanistic cascade of apoptosis induction by FLT3-ITD inhibitors and homoharringtonine (HHT).

FLT3-ITD, Axl and IL-3 receptor inactivate GSK3b and increase Mcl-1 protein to block apoptosis. FLT3-ITD inhibitors activate GSK3b by inhibiting FLT3-ITD and Axl and then decrease Mcl-1 protein level. HHT decreases the protein levels of Mcl-1, FLT3-ITD and Axl, and enhances FLT3-ITD inhibitor-induced apoptosis.