The role of angiogenesis in the biology and therapy of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow that morphologically shows trilineage dysplasia. Mechanisms of disease include pluripotent stem cell damage, abnormalities in proliferation, differentiation, and apoptosis leading to an ineffective hematopoiesis. A growing body of evidence support angiogenesis as having a key role in the pathophysiology of hematologic malignancies, including MDS. Knowledge and interest in angiogenesis and its interactions with proliferation and apoptosis have provided the rationale for the use of antiangiogenic drugs, such as thalidomide and its analogue CC5013, with hematologic improvement. Although the results are modest, other drugs with somewhat novel antiangiogenic mechanisms of action are under development, such as the vascular endothelial growth factor-receptor blocker SU5416, the antivascular endothelial growth factor antibody bevacizumab, arsenic trioxide, metalloproteinase inhibitors, such as AG3340, and farnesyl transferase inhibitor R115777. This review attempts to provide an overview of the evidence of increased angiogenesis and the status of drug development targeting angiogenesis in patients with MDS.