Role of VEGF/VEGFR in the pathogenesis of leukemias and as treatment targets (Review).

Angiogenesis plays an important role in solid tumor growth, progression and metastasis. Evidence suggests that the progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation under the influence of acute leukemia, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma and lymphomas. The vascular endothelial growth factor (VEGF) is the most important proangiogenic agent that activates receptors on vascular endothelial cells and promotes blood vessel regeneration. It has been demonstrated that VEGF/VEGF receptor (VEGFR) expression is upregulated in several types of hematolymphoid tumor cells accompanied with angiogenesis. The levels of VEGF/VEGFR are correlated with the treatment, relapse and prognosis of hematolymphoid tumors. In order for VEGF family and their receptors as antiangiogenic targets to treat solid tumors, several antiangiogenic agents targeting VEGF-related pathways have been used for the treatment of hematolymphoid malignancies in clinical trials. The results demonstrate a promising therapeutic intervention in multiple types of hematolymphoid tumors. This review aims to summarize recent advances in understanding the role of VEGF and angiogenesis in leukemias, mainly focusing on their upstream transcriptors, downstream targets and the correlation of VEGF/VEGFR with the treatment, relapse or prognosis of leukemia. The progress of VEGF and its receptors as attractive targets for therapies are also discussed in clinical application.