Autocrine VEGF loops, signaling pathways, and acute leukemia regulation

Data obtained from animal models, and partially confirmed in pre-clinical studies, have provided clear evidence of the importance of angiogenesis for the growth of solid tumors. Similarly, in hematological cancers such as leukemias and lymphomas, the role of angiogenesis has been under intense scrutiny. However, the molecular singularities of leukemia, namely its cellular origin, have suggested a putative role for angiogenesis in these tumors may have distinct features. We and others have shown acute leukemia cells use angiogenic growth factor signaling pathways, namely those activated by vascular endothelial growth factor (VEGF) in autocrine and paracrine fashion. Autocrine and paracrine VEGF stimulation of subsets of leukemias results in cell proliferation, increased survival and migration. This review discusses recent advances in the field of leukemia angiogenesis, focusing on the role of VEGF and its receptors, acting in a paracrine or autocrine manner. We also briefly describe some of the novel anti-angiogenic compounds, namely VEGF blockers, and suggest their use to treat subsets of hematological malignancies may have clinical benefit.