3205 – LIMS1 REGULATES ACUTE MYELOID LEUKEMIA INITIATION THROUGH CELL-ADHESION INTERACTIONS OF LEUKEMIC STEM CELLS

Acute myeloid leukemia (AML) long-term survival remains particularly poor due to the inability to eliminate leukemic stem cells (LSCs) capable of initiating and maintaining the disease. In this study, leveraging a previously generated single-cell transcriptomic atlas of AML-LSCs, we have identified LIMS1 as an important regulatory gene in AML-LSCs. Our findings demonstrate that functional targeting of LIMS1 (via CRISPR- and shRNA-mediated approaches) disrupts the proliferation and clonogenicity of AML cell lines and primary human samples in vitro, while also diminishing engraftment capacity and impeding disease progression in vivo upon transplantation into immunocompromised mice. Moreover, the absence of LIMS1 markedly attenuates the migration and invasion capacity of AML cells in vitro and compromises their ability to home to the bone marrow (BM) niche in in vivo homing assays. Notably, reduced colonization of distant sites is observed upon direct transplantation of AML cells into the BM. RNA-seq analysis further suggests a gene expression signature indicative of altered migration and cell adhesion in LIMS1-deficient AML cells. These findings align with the established role of LIMS1, an adaptor protein positioned at the nexus of integrins and growth factor receptors signaling, in mediating cell adhesion and migration processes. Our study elucidates a critical role for LIMS1 in governing AML-LSC function through modulation of cell adhesion and migration processes, thereby unveiling potential new therapeutic avenues for AML.