biostudies-literatureGambi GStanford Genome Technology CenterAlex's Lemonade Stand Foundation for Childhood CancerSt. Baldrick's FoundationItalian Association for Cancer ResearchNational Cancer InstituteNCI NIH HHSNational Institutes of HealthNational Cancer Institute Division of Cancer PreventionHopkins Population Center, Johns Hopkins UniversityAmerican-Italian Cancer Foundation42-60.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC11934262biostudies-literatureUnknown85(1)Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response. Single-cell mapping reveals heterogeneous gene activation in discrete epigenetic clones, aiding in patient stratification for relapse risk after chemotherapy. Finally, we identify MYB as a 3D hub regulatorMolecular cell3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.PMC11934262R01 CA266212R01CA252239P01CA229086P30 CA008748R01 CA140729RO1CA29815326533R01 CA252239R01 CA271455R01CA271455P01 CA229086R01 CA298153R01 CA228135P30 CA016087R01CA140729R01CA266212R01CA228135R01CA260028R01 CA260028Apostolou ETan JBoccalatte FAifantis IAvrampou KLin ZTsirigos AGambi GNadorp BRodriguez Hernaez JKentsis APolyzos AInghirami Gfalse3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response. Single-cell mapping reveals heterogeneous gene activation in discrete epigenetic clones, aiding in patient stratification for relapse risk after chemotherapy. Finally, we identify MYB as a 3D hub regulator2025-01-01T00:00:00Z2025 Jan2026-06-06T19:56:38.042Z2026-06-04T03:12:28.011ZS-EPMC119342623971970510.1016/j.molcel.2024.11.040