PK11195, a peripheral benzodiazepine receptor ligand, chemosensitizes acute myeloid leukemia cells to relevant therapeutic agents by more than one mechanism.

Like Bcl-2, peripheral benzodiazepine receptors (pBzRs) reside in mitochondrial pores, are frequently over-expressed in tumor cells, and can protect cells from apoptotic cell death. We now show that the high-affinity, pBzR-specific ligand, PK11195, chemosensitizes AML cells to relevant chemotherapeutics, but is relatively non-toxic as a single agent, and does not chemosensitize normal myeloid cells. PK11195 can block p-glycoprotein efflux in AMLs, contributing to increased daunomycin toxicity in efflux-competent AMLs, but can also sensitize AMLs to cytarabine and DNR-sensitize efflux-incompetent AMLs, presumably via mitochondrial pore effects documented in other models. Therefore, PK11195 might contribute to improved clinical outcomes in AML.