Dopamine receptor allows selective targeting of neoplastic progenitors in human acute myeloid leukemia

Dopamine receptor (DRD) antagonist thioridazine (TDZ) has been traditionally prescribed as an anti-psychotic drug. Recent observations have revealed anti-neoplastic effects of TDZ in a variety of neural and non-neural cancers including acute myeloid leukemia (AML). However, the basis of TDZ effects on transformed tissues is not fully understood. We used AML as a model system to study the anti-neoplastic properties of TDZ, as well as the downstream mechanism of action for DRDs in the context of cancer. Our study defines a role for DRDs in regulating neoplastic properties and suggests DRD2 as an attractive therapeutic target for AML. Xenografted AML samples were obtained after in vivo treatment with Thioridazine (TDZ) for 21 days. The human leukemic cells (hCD45+CD33+) were FACS-purified and RNA was extracted. Gene expression profiles were compared between TDZ- versus vehicle (captisol 30%)-treated matched xenografts.