Search

Simple Summary: In chronic lymphocytic leukemia (CLL), abnormal B lymphocytes accumulate in the bone marrow (BM) and secondary lymphoid tissues. The BM and lymph nodes support angiogenesis and increased vascularization. Although certain drugs approved by the US Food and Drug Administration improve clinical outcomes, some patients do not respond and others relapse. Interactions between CLL cells and the tissue microenvironment favor leukemic cell trafficking, survival, and proliferation via the production of soluble factors. Some of these factors exhibit pro-angiogenic properties. This review summarizes the biology of these molecules with survival/pro-angiogenic value, and provides a summary of new, selective inhibitors targeting these molecules (and their receptors) currently under evaluation in preclinical and clinical studies. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogenic factors in CLL. A number of other CLL factors might have pro-angiogenic activity: fibroblast growth factor-2, certain chemokines (such as CXCL-12 and CXCL-2), tumor necrosis factor-α, insulin-like growth factor-1, neutrophil gelatinase-associated lipocalin, and progranulin. All these molecules contribute to the survival, proliferation, and migration of CLL cells. Here, we review the literature on these factors' respective expression profiles and roles in CLL. We also summarize the main results of preclinical and clinical trials of novel agents targeting most of these molecules in a CLL setting. Through the eradication of leukemic cells and the inhibition of angiogenesis, these therapeutic approaches might alter the course of CLL. [ABSTRACT FROM AUTHOR]