Figure 5. Proposed model of TGF-β pathway activity in bone marrow failure and MDS.

Either excessive or insufficient TGF-β signaling is deleterious. In SDS, the TGF-β pathway is hyperactivated, which inhibits hematopoiesis. TGF-β inhibitors relieve the hyperactivated state of TGF-β signaling in SDS, resulting in improved hematopoiesis. Because the TGF-β pathway activity is relatively lower in SDSdel(7q), reduction of TGF-β signaling results in insufficient TGF-β pathway activity and inhibits outgrowth of these cells.