A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia - PubMed
3 hours ago
- #acute myeloid leukemia
- #combination therapy
- #epigenetics
- Perturb-seq screening identifies a synergistic epigenetic hub (KAT6A, Menin, DOT1L) that silences a core myeloid differentiation program in KMT2A-rearranged AML.
- Simultaneous pharmacological inhibition of hub components robustly reactivates the myeloid program, showing synergistic anti-leukemic effects.
- The myeloid program serves as a predictive biomarker; high baseline activity indicates vulnerability to MEK, AKT, and mTOR inhibitors.