Targeted Combination Therapy to Eradicate Leukemia Stem Cells in Chronic Myeloid Leukemia (CML). The oncogenic BCR-ABL fusion protein phosphorylates and activates STAT5, which initiates a pathway leading to quiescence of leukemia stem cells. Tyrosine kinase inhibitors block BCR-ABL, whereas pioglitazone activates peroxisome proliferator-activated receptor gamma (PPARγ), which inhibits STAT5. The synergistic effect of both drugs on the quiescence pathway leads to the death of the leukemia stem cells.