Bone marrow effects of antivascular agents for leukemia treatment. Vascular disrupting agents (basic structure of OXi4503 shown at the bottom left) can mediate their antileukemic effects through multiple mechanisms. First, the agents directly target the endothelial cells and destroy vasculature; this represents an indirect antileukemic activity by decreasing the supply of oxygen and nutrients and abrogating the supportive function of endothelial cells on leukemia cells. The influence of endothelial cells on vascular stem cell niches will then be particularly important. Second, the agents may have additional and direct effects on the AML cells. Finally, the antileukemic efficiency must be weighted against the risk and severity of bone marrow toxicity including suppression of remaining normal hematopoietic cells.