Furthermore, both genetic and pharmacologic inhibition of HIF1α suppressed MDS development with only mild effects on normal hematopoiesis, implicating HIF1α signaling as a promising therapeutic target to tackle the heterogeneity of MDS.<i>Cancer Discov; 8(11); 1355-7.
These findings reveal HIF1A as a central pathobiologic mediator of MDS and as an effective therapeutic target for a broad spectrum of patients with MDS.<b>Significance:</b> We showed that dysregulation of HIF1A signaling could generate the clinically relevant diversity of MDS phenotypes by functioning as a signaling funnel for MDS driver mutations.
Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload.