The Instructive Role of the Bone Marrow Niche in Aging and Leukemia

In this review, we aim to discuss the role of the bone marrow microenvironment in supporting hematopoiesis, with particular focus on the contribution of the endothelial niche in dictating hematopoietic stem cell (HSC) fate.

Evidence gathered in the past two decades revealed that specific cell types within the bone marrow niche influence the hematopoietic system. Endothelial cells have emerged as a key component of the HSC niche, directly affecting stem cell quiescence, self-renewal, and lineage differentiation. Physiological alterations of the bone marrow niche occurring in aging have been described to be sufficient to promote functional aging of young HSCs. Furthermore, a growing body of evidence suggests that aberrant activation of endothelial-derived signaling pathways can aid or trigger neoplastic transformation.

Several groups have contributed to the characterization of the different cell types that comprise the complex bone marrow environment, whose function was long perceived as an undiscernible sum of many parts. Further studies will need to uncover niche cell-type-specific pathways, in order to provide new targets and therapeutic options that aim at withdrawing the microenvironmental support to malignant cells while sparing normal HSCs.