A novel peptide and its mechanism overcoming imatinib-resistance chronic myeloid leukemia

COG133, a peptide inhibitor of SET, can enhance PP2A activity to treat imatinib-resistant CML by T315I mutation. Based on this fact, a peptide designated as SP2 showed the best anti-tumor activity among nine newly-designed Apolipoprotein E-mimetic peptides compared to COG133. The IC₅₀ of SP2 against BaF3-p-210(T315I)cells was(2. 9±0. 1)μmol/L at 72 h, 10% of that of COG133(26. 5±1. 2 μmol/L). Further studies indicated that SP2 antagonizes SET protein to increase the activity of PP2A, thereby dephosphorylating p-BCR-ABL to induce cell apoptosis.