Rewiring the Leukemic Genome: 3D Chromatin Architecture in B-cell Acute Lymphoblastic Leukemia.

Three-dimensional genome organization shapes gene regulation during normal B-cell development, and its disruption contributes to the initiation and progression of B-cell acute lymphoblastic leukemia. Through multi-omic studies, Ghebrechristos and colleagues revealed that transcription factors, including ERG in ETV6::RUNX1 leukemia, remodel chromatin interactions to sustain oncogenic gene expression programs, identifying genome architecture as both a driver of leukemogenesis and a potential therapeutic vulnerability. See related article by Ghebrechristos et al., p. 586.