A Novel Thiadiazolidine-Dione Targets Human Leukemia Stem Cells

Leukemia stem cells (LSCs) are a small population of malignant cells known to initiate and maintain leukemia. LSCs have been identified for AML, CML and ALL. Unfortunately, there is increasing evidence demonstrating that LSCs are not effectively destroyed by standard chemotherapy regimens. Failure to eradicate LSCs is likely to result in disease relapse. Therefore, novel therapies that can destroy LSCs are urgently needed to prevent relapse and improve patient survival. We have identified a compound [4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8)] that can induce rapid and irreversible cell death in leukemia cells including progenitor and stem cell populations without harming normal blood cells. TDZD-S has been previously studied for cell protective functions in animal models for treatment of different diseases including Alzheimer's, colitis and stroke. However, we have identified a unique anti-leukemia effect for this agent that can be observed with a very short exposure to the drug (5-30 minutes). Therefore, the objective of this proposal is to study and improve the properties ofTDZD-8 for leukemia therapy.