Resistance to FLT3 inhibitors in acute myeloid leukemia: Molecular mechanisms and resensitizing strategies

Figure 1 Schematic representation of various published mechanisms of resistance to FMS-like tyrosine kinase 3 inhibitors. This figure shows a number of models of resistance including desensitization of drug targets by FLT3 gene amplification or protein overexpression, decreased drug binding affinity by mutation, deletion or insertion in TKD, increased drug efflux by p-gp, activation of survival and proliferative pathways (molecules) such as RAS pathway, STAT pathway, anti-apoptotic Bcl-xL, Survivin and DNA repair molecule RAD51. FLT3: FMS-like tyrosine kinase 3; TKD: Tyrosine kinase domain; STAT: Signal transducer and activator of transcription.