As we and others (3, 40) have shown previously, AML and ALL patients' marrows, but not healthy BM, become profoundly hypoxic at the intracellular level, which leads to stabilization of main transcriptional regulator of hypoxia HIF-1α and its downstream targets such as CA9 in leukemia cells, despite ample oxygen delivery through the vasculature. Here, HIF1A is linked to acute myeloid leukemia.