This study proposes a novel therapeutic paradigm for Acute Myeloid Leukemia (AML) by targeting the bioelectric state of malignant cells. Using a high-accuracy neural network (>98%), we identified the LOC401317-KCNJ15 axis as a critical regulator of cell membrane potential and innate immune response. By integrating Connectivity Map (CMap) pharmacogenomics and Quantitative Systems Pharmacology (QSP) modeling via PhysiCell, we compared two intervention strategies: Pharmacological: Metabolic reprogramming using Rosiglitazone, which showed cytostatic but limited efficacy. Genetic: Targeted CRISPRa activation of the silenced LOC401317/KCNJ15 axis. Our in silico results demonstrate that bioelectric repolarization via CRISPRa-mediated gene activation completely eradicates the tumor population by reversing tumor-induced immunosuppression. This work provides a mechanistic roadmap for transitioning from computational models to in vitro assays, highlighting non-canonical bioelectric pathways as promising targets for leukemia treatment.
María Victoria Maldonado Bao (Fri,) studied this question.