Angiogenesis in Hematologic Malignancies

Abstract

Angiogenesis is defined as the production of new blood vessels from an existing vascular network. It is important in a variety of physiologic and pathologic disorders. It is active during development but is relatively quiscent during normal adult life.

Angiogenic factors include direct angiogens, indirect angiogens, and integrins. Direct angiogens stimulate the formation of new blood vessels directly. Indirect angiogens promote neovascular formation by paracrine stimulation of direct angiogens. Integrins mediate interactions between the developing vessels and components of the extracellular matrix. A variety of circulating and sequestered inhibitors suppress proliferation of vascular endothelium under normr.l conditions. As a result, endothelial cells are among the most quiescent cells of the body.

Tumors can exist for months or years without neovascularization. However, with clonal progression, subsets of the tumor population may undergo a switch to an angiogenic phenotype. This switch involves a change in the local balance between pro- and antiangiogenic factors. Tumors unable to induce angiogenesis remain dormant at a microscopic in situ size. Such nonangiogenic lesions are usually not detectable unless they are on external surfaces such as skin, oral mucosa, or cervix. Recently, however, it has become clear that angiogenic factors play an important role in the pathophysiology of many hematological disorders. Bone marrow angiogenesis was subsequently found to correlate with multiple myeloma progression, and was also observed in lymph nodes of B cell non-Hodgkiri