Historically, TCF3::PBX1-positive leukemia has been associated with a poor prognosis, but this has been overcome by modern therapy regimens and TCF3::PBX1 currently defines a group of ALL patients with a good clinical outcome in childhood ALL16,6–9, although these patients appear to have an increased risk for CNS involvement at diagnosis10. Here, TCF3 is linked to acute lymphoblastic leukemia.