Here, we show that PtPT-induced UPS inhibition leads to caspase-3-mediated onset of apoptosis in both IM-resistant and IM-sensitive CML cells and that both UPS inhibition and caspase activation are required for PtPT to induce Bcr-Abl downregulation. The gene discussed is PTPN2; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.