Kindlin-3 loss curbs chronic myeloid leukemia in mice by mobilizing leukemic stem cells from protective bone marrow niches
Peter W. Krenn, Steffen Koschmieder, Reinhard Fässler
Abstract
Significance Current leukemia treatments focus on targeting leukemic cells and neglect the influence of the malignant BM environment, which is modified to nurture and protect LSCs. By abrogating K3-mediated integrin adhesion of LSCs to BM niches, either through genetics or an LSC-specific RNA aptamer-mediated K3-siRNA delivery, we impaired integrin-mediated niche retention of LSCs, slowed down the course of leukemia in vivo, and prolonged the survival of mice suffering from CML. Therefore, delivering K3-depleting compounds via tumor-specific surface receptors represents a strategy to abolish the function of multiple integrin classes on LSCs and interactions with numerous niche components at once.