Mechanistically, we observed that HIF2α promotes expression of transcriptional repressors/corepressors (i.e., RUNX2 and BCL11A) that suppress myeloid differentiation genes in AML (Kuo et al, 2009; Sunami et al, 2022), suggesting that differentiation blockade by HIF2α occurs via regulation of transcriptional repressive programs. This evidence concerns the gene EPAS1 and acute myeloid leukemia.