Indeed, exploiting the distinctive hypoxia aspects and the hypoxia-dependent component such as HIF-1α or the angiogenesis factor VEGF in the context of hematological neoplasms and, in this specific manuscript, in ALL, represents a promising challenge to improve the current treatment scenario, selecting the optimal drug doses to reduce side effects and overcoming drug resistance. The gene discussed is VEGFA; the disease is acute lymphoblastic leukemia.