Targeting leukemic stem cell biomechanics suppresses stemness and enhances NK cell-mediated immunotherapy.

ABSTRACT: Acute myeloid leukemia (AML) is primarily driven by leukemic stem cells (LSCs), the main cause of relapse and therapy resistance. Here, we discover that LSCs are predominantly small and mechanically soft. These mechanical properties enable their selective isolation using microfluidic chips. Single-cell RNA-sequencing of primary human AML bone marrow identifies enrichment of LSCs within the FSC^low ALDH1A1⁺ subpopulation, which exhibits long-term stemness in functional assays. Notably, inhibiting ALDH1A1 in these cells promotes F-actin polymerization and increases cellular stiffness, reducing their stemness while enhancing their susceptibility to natural killer (NK) cell-mediated cytotoxicity. In AML patient-derived xenograft models, the combination of ALDH1A1 inhibitio

SUBMITTER: Zhu M 

PROVIDER: S-EPMC12669726 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature