Effect of Flt3-ITD on PLZF and ETO association with SMRT. (A) Normal cells, PLZF and ETO, both interact with SMRT and function to repress transcription. (B) In leukemia, expression of Flt3-ITD results in the enhancement of the binding of nuclear-cytoplasm shuttling protein p65 and SMRT, which enhances nuclear export of SMRT. This plays a role in dissociation of SMRT from nuclear transcriptional repressors, altering gene regulation and growth control in the leukemic cell.