Biology of BM failure syndromes: role of microenvironment and niches.

The BM microenvironment and its components regulate hematopoietic stem and progenitor cell (HSC) fate. An abnormality in the BM microenvironment and specific dysfunction of the HSC niche could play a critical role in initiation, disease progression, and response to therapy of BM failure syndromes. Therefore, the identification of changes in the HSC niche in BM failure syndromes should lead to further knowledge of the signals that disrupt the normal microenvironment. In turn, niche disruption may contribute to disease morbidity, resulting in pancytopenia and clonal evolution, and its understanding could suggest new therapeutic targets for these conditions. In this chapter, we briefly review the evidence for the importance of the BM microenvironment as a regulator of normal hematopoiesis, summarize current knowledge regarding the role of dysfunctions in the BM microenvironment in BM failure syndromes, and propose a strategy through which niche stimulation can complement current treatment for myelodysplastic syndrome.