To explore the HIF-α dependency of the anti-leukemic effect of IOX5, we treated control and Hif1/2aDKO cells with IOX5 and found that control AML cells manifest substantially reduced proliferation, whereas Hif1/2aDKO cells are refractory to IOX5 and proliferate normally (Fig. 7b), indicating that IOX5 requires the intact HIF system to exhibit its anti-leukemic activity. The gene discussed is HIF1A; the disease is acute myeloid leukemia.