Bone marrow niche in the myelodysplastic syndromes

Abstract

The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow (BM) failure, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia (AML). The BM microenvironment in MDS plays an important role in the development of this disorder. The BM stromal cells of MDS patients often harbor distinct chromosomal aberrations than the hematopoietic elements, suggesting different genetic origins. Perturbed cytokine secretions from BM stromal cells such as multipotent mesenchymal stem cells (MSCs) and endothelial cells are associated with increased proliferation and survival of malignant hematopoietic cells. Within the MDS BM there are also alterations in stromal cell composition, signaling and angiogenesis between Low- and High-risk MDS patients. Several open lines of investigation into the MDS niche remain, including the timing of stromal defects in context to dysplastic hematopoiesis. Another important, unanswered question is the impact of age on BM stroma function and regulation (or dysregulation) or hematopoietic stem/progenitor cells. With a better understanding of the MDS niche, new therapeutic strategies will emerge.

Keywords: Bone marrow niche; Endothelial cells; Hematopoietic stem cells; Mesenchymal stem cells; Myelodysplastic syndromes.