Because ALL typically involves mutations (PAX5-altered), complex rearrangements (e.g., DUX4-rearranged, PAX5-altered, ZNF384-rearranged), and/or oncogenic gene fusions (e.g., ETV6::RUNX1, TCF3::PBX1, KMT2A-rearranged) of transcription factor (TF) genes, as well as disruptions of cis-regulatory elements,8 chromatin-accessibility maps can provide valuable information to better understand the leukemogenic process. The gene discussed is TCF3; the disease is acute lymphoblastic leukemia.