Multifaceted pharmacologic targeting of FLT3-ITD via gene silencing, protein kinase inhibition and protein degradation. (A) Proteasome inhibitors disrupt the microRNA-29 (miR-29)/Sp1/nuclear factor κB (NF-κB) regulatory mechanisms of FLT3 gene transcription.^5-7  (B) TKI inhibits FLT3 protein tyrosine kinase activity. (C) Proteasome inhibitors induces autophagy gene 5 (ATG5)/ATG12/ATG13-mediated autophagy, autophagosome formation (as indicated by the conversion of protein 1 light chain 3 [LC3-I] to LC3-II), and cargo protein–mediated FLT3-LC3 binding that ensure autophagic target degradation.⁸  P, phosphorylation.