High-throughput Perturb-seq identifies the Myeloid Program as a key prognostic biomarker in KMT2A-rearranged AML, suggesting new therapeutic strategies.
Key Points
To map the epigenetic network in KMT2A-rearranged AML and identify vulnerabilities for targeted therapies.
High-throughput Perturb-seq screen on KMT2A-r AML cell line MOLM-13
Computational modeling to identify transcriptional modules
Validation through pharmacological inhibition, bulk RNA-sequencing, and clinical correlation analyses.
Identified the Myeloid Program as a key regulator silenced by an epigenetic repression circuit.
Demonstrated synergistic anti-leukemic activity through dual inhibition of KAT6A and Menin.
High Myeloid Program activity correlates with improved overall survival, identifying it as a prognostic biomarker.