Normal cells maintain homeostasis by tightly regulating intracellular trafficking of ions, small molecules and proteins. (A) Proteins located predominantly in the nucleus are able to function normally (eg, SET is able to activate its target PP2A, a tumor suppressor). (B) Leukemic transformation abrogates the trafficking of cargo with inappropriate diversions provided by upregulated karyopherins, such as XPO1, providing the “green light” to export specific proteins out of the nucleus. Protein activity is altered (eg, PP2A is no longer appropriately activated). (C) KPT-300 with imatinib treatment introduces a “red light” to halt subverted proteins from being diverted from the nucleus, and nuclear proteins are able to function within their appropriate context.