In Silico Discovery of Permethrin-Driven Myeloid Leukemogenesis: Molecular Mechanisms and Public Health Implications

The rising global incidence of myeloid leukemias [acute myeloid leukemia (AML)/chronic myeloid leukemia (CML)] and unresolved debates about permethrin’s leukemogenic potential necessitate mechanistic insights into its molecular interactions. This study integrates multiomics data, deep learning, and computational toxicology to investigate permethrin’s role in AML/CML pathogenesis. Dual deep learning models (DeepPurpose and DMFF-DTA) enhanced target prediction accuracy (composite scores >13), while system analyses linked permethrin to PI3K-Akt and Rap1 pathway dysregulation. Molecular docking, 100-ns dynamics simulations, and molecular mechanics/Poisson–Boltzmann surface area identified STK10 (ΔGbinding = ‒28.77 kcal/mol) and AKR1B1 (ΔGbinding = −20.24 kcal/mol) as high-affinity targets, with van der Waals and electrostatic forces driving stability. Single-cell transcriptomics revealed STK10’s prominence in AML-associated immune cells and AKR1B1’s enrichment in CML precursor B cells. Findings suggest permethrin drives leukemogenesis through multitarget mechanisms, with STK10 and AKR1B1 serving as critical AML- and CML-specific effectors, respectively. The study proposes biomonitoring permethrin metabolites in high-risk populations and advocates regulatory measures to limit lipophilic formulations (logP >5). The findings of this study highlight the significant toxicological and mechanistic implications of permethrin exposure in the development of myeloid leukemias, offering new directions for future research. By integrating computational techniques with public experimental data, this study provides a comprehensive understanding of the potential pathobiological impact of permethrin on AML and CML. While in silico evidence supports permethrin’s pathogenic role, experimental validation using gene-edited models is warranted to confirm therapeutic targets in future studies. This computational framework advances environmental carcinogen screening and underscores the need for molecular-level surveillance in precision public health, balancing agricultural benefits against latent leukemia risks.