HIF-1α and HIF-2α interact with the “hypoxia-responsive elements” (HREs) of various genes (e.g., TGF-β, c-Kit, FGF-2, VEGF, and Notch-1) which may upregulate the expression of CXCR4 and CXCL12 on AML cells and ECs, thereby promoting LSC maintenance and chemotherapy resistance [139]. Here, EPAS1 is linked to acute myeloid leukemia.