VEGF targeted therapy in acute myeloid leukemia.

The cooperation of two classes of mutations in hematopoietic cells is hypothesized in a multistep pathogenesis model of acute myeloid leukemia (AML). Class I mutations confer a proliferative and/or survival advantage, whereas Class II mutations block hematopoietic differentiation and impair apoptosis in AML cells. In addition to these two classes of mutations, a relevant role for angiogenesis in the pathophysiology of AML has been recently proposed. The recognition that the vascular endothelial growth factor (VEGF) pathway is a key regulator of angiogenesis has led to the development of several VEGF-targeted approaches. These include neutralizing antibodies, VEGF traps or selective tyrosine kinase inhibitors for VEGFRs. Other drugs that indirectly affect VEGF pathway, such as statins or arsenic trioxide, also have been shown to possess antiangiogenic activity in leukemias. The benefits of these VEGF targeted agents and their current stage of development as novel anti-antiangiogenic therapies in AML are discussed in this review.