The dynamic interaction of pediatric ALL cells and MSCs: influencing leukemic cell survival and modulating MSC β-catenin expression.

Abstract

Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization. In this study, we compared BM-MSCs derived from pediatric ALL patients with those from matched healthy donors (HDs). Our results indicate that while both ALL-MSCs and HD-MSCs meet the criteria established by the International Society for Cellular Therapy, they exhibit significant differences in proliferation and differentiation capacity. ALL-MSCs displayed markedly lower proliferation rates and reduced osteogenic/adipogenic differentiation potential compared to HD-MSCs. Furthermore, co-culture experiments revealed that MSCs enhance the survival of leukemic blasts through both soluble factors and direct cell-cell interactions, underscoring their anti-apoptotic properties. Importantly, our findings demonstrate that interactions with leukemic cells activate the Wnt/β-catenin signaling pathway in MSCs, suggesting a potential target for therapeutic intervention. Overall, this study enhances our understanding of the role of BM-MSCs in leukemia and highlights β-catenin as a promising target for future therapies.