Inhibition of HIF1α Signaling: A Grand Slam for MDS Therapy?

The recent focus on genomics in myelodysplastic syndromes (MDS) has led to important insights and revealed a daunting genetic heterogeneity, which is presenting great challenges for clinical treatment and precision oncology approaches in MDS. Hayashi and colleagues show that multiple mutations frequently found in MDS activate HIF1α signaling, which they also found to be sufficient to induce overt MDS in mice. 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.