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

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. Overall design: 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.