DNTTIP1 Drives Leukemogenesis Through HDAC1-Dependent Epigenetic Silencing of BMF [RNA-Seq, 1]

Here, we uncover deoxynucleotidyl transferase terminal-interacting protein 1 (DNTTIP1) as a previously unrecognized epigenetic regulator crucial for the survival of leukemic cells. Mechanistically, depletion of DNTTIP1 impairs histone deacetylase 1 (HDAC1) recruitment to chromatin, leading to hyperacetylation of histone H3 lysine 27 (H3K27) at the promoter of BCL2 modifying factor (BMF) and reactivating this pro-apoptotic effector.

The upregulated BMF competitively disrupts BCL2-mediated survival pathways, triggering coordinated autophagy and apoptosis. This dual cell death mechanism is critical for leukemia suppression. Our preclinical evidences demonstrate that combined HDAC1 and BCL2 inhibition exerts synergistic anti-leukemic effects, a therapeutic strategy currently under clinical evaluation.