Schematic representation of ST1926 repression of Tax and apoptosis of ATL cells. Tax expression induces oligoclonal expansion of HTLV-1–infected CD4 T cells and deregulates signaling pathways including p53-p21 or DNA repair. ATL monoclonal proliferation occurs after decades of evolution in 2% to 7% of HTLV-1–infected patients. Cells having shut down Tax expression escape anti-Tax cytotoxic T lymphocytes and are preferentially selected. ATL cells have a Tax-negative and HBZ-positive phenotype. Transient or low-level Tax expression occurs, particularly in leukemia-initiating cells. ST1926 downregulates Tax expression and reactivates the p53-p21 signaling pathway. ST1926 induces massive and p53-independent apoptosis of leukemic cells.