Microenvironment In

The hematopoietic microenvironment refers to the fibroblasts, adipose cells, macrophages, endothelial cells, and the supportive matrix of the bone marrow.56 Though still somewhat controversial, there is growing evidence that abnormalities of the supporting stroma affect its ability to effectively support normal hematopoiesis in MDS.56-59

Using in vitro studies, abnormalities of the hematopoi-etic microenvironment in patients with MDS were demonstrated.60 Adherent cell layers were developed in long-term bone marrow cultures (LTMC) from MDS patients and normal marrows. The adherent cell layer consisted of a mixture of cells, mostly fibroblasts and macrophages. Morphologically, the adherent cell layer appeared to be normal in MDS, however, it produced more IL-6 and TNF compared to normal bone marrow. The adherent cell layers were then separated into macrophage, and fibroblast-enriched cell layers, both of which demonstrated increased apoptosis. The macrophage-enriched cell layer produced significantly higher TNF-a, while the fibroblast-enriched layer produced significantly higher IL-6 than normal marrows. A dysfunctional stroma may also contribute to the patho-genesis of MDS. Reports of donor cell leukemia or MDS after allogeneic stem cell transplant may represent supporting evidence for the role of the microenvironment and stroma in disease pathogenesis.61

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