Bcl11a sustains DN2 thymocyte competition to avert thymus autonomy and T-ALL (scRNA+TCR-seq)

T-cell acute lymphoblastic leukaemia (T-ALL) arises when thymic checkpoints fail, yet their molecular guardians are unknown. We show that haematopoietic deletion of the zinc-finger factor Bcl11a precipitates a rapidly fatal, transplantable T-ALL bearing hotspot Notch1 and Arid1a lesions that mirror the human disease. Multi-omic and mosaic analyses reveal that Bcl11a, together with Runx1, maintains a progenitor transcriptional programme, restrains T-lineage genes and endows DN2 thymocytes with the competitive fitness required to suppress thymus autonomy.