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0The research examines how the spatial positioning of leukaemic stem cells (LSCs) within different bone marrow regions fundamentally dictates their survival and disease progression. Studies using mouse models demonstrate that LSCs remain quiescent and stem-like when localized in the metaphysis, whereas moving to the central marrow induces cell-cycle activity and therapeutic vulnerability. This localization is controlled by a complex chemical signaling axis involving the enzymes DPP4 and GPC3, which regulate gradients of the chemoattractant CXCL12. Specifically, DPP4 deficiency or inhibition disrupts these gradients, forcing LSCs out of their protective niches and trapping them within the bone marrow to prevent systemic spread. The researchers conclude that targeting this regulatory pathway causes LSC exhaustion and significantly enhances the effectiveness of acute myeloid leukaemia treatments. By identifying N-cadherin+ stromal cells as the key producers of these supporting signals, the study offers a precise roadmap for future clinical interventions.
References:
Wang C, Pan Y, Dong R, et al. Longitudinal localization of leukaemic stem cells between the metaphysis and central marrow governs their behaviour[J]. Nature Cell Biology, 2026: 1-13.
