Altered mesenchymal niche cells impede generation of normal hematopoietic progenitor cells in leukemic bone marrow

摘要: Degeneration of normal hematopoietic cells is a shared feature malignant diseases in the system. Previous studies have shown exhaustion progenitor (HPCs) leukemic marrow, whereas stem (HSCs) remain functional upon relocation to non-leukemic marrow. However, underlying cellular mechanisms, especially specific niche components that are responsible for degeneration HPCs, unknown. In this study, we focused on murine bone mesenchymal (MSCs) and their supporting function Notch1-induced acute T-cell lymphocytic leukemia (T-ALL) mice. We demonstrate proliferative capability differentiation potential T-ALL MSCs were impaired due accelerated senescence. RNA-seq analysis revealed significant transcriptional alterations MSCs. After co-cultured with from mice, inhibitory effect HPCs was defined, vivo repopulating HSCs not compromised. Furthermore, osteoprotegerin identified as cytokine improve enhance HPC output via p38/ERK pathway. Therefore, study reveals novel mechanism inhibition generation T-ALL. Leukemic may serve target improving regeneration therapeutically.