We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T?cell receptor (TCR) ? enhanceosome activity and blocked TCR-J? rearrangement.     ///    TLX1/TLX3 abrogation or enforced TCR?? expression leads to TCR? rearrangement and apoptosis.     ///    "Importantly, the autoextinction of clones carrying TCR?-driven TLX1 expression supports TLX ""addiction"" in TLX-positive leukemias and provides further rationale for targeted therapy based on disruption of TLX1/TLX3.. "