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Regulation and function of angiogenic factors in chronic lymphocytic leukemia

摘要Progression of chronic lymphocytic leukemia (CLL) is determined by the localization of malignant cells in lymphoid tissues, where they receive growth and survival signals. CLL cells produce angiogenic factors that are regulated by internal and external stimuli and whose levels vary according to the clinical stage of the disease. Stromal cellular and molecular components in CLL niches disturb the balance of pro- and antiangiogenic molecules in CLL cells and induce an angiogenic switch. Additionally, CLL cells also influence the behavior of microenvironmental cells, inducing endothelial cell proliferation and increasing the angiogenic capacity of macrophages, neutrophils, and other cells present in CLL niches. As a result of these reciprocal functional interactions, bone marrow angiogenesis is frequently increased in CLL and has been proposed as a prognostic marker in early disease. Besides their role in regulating angiogenesis, angiogenic factors are also involved in CLL cell migration and survival, all contributing to disease progression. Angiogenic factors, particularly vascular endothelial growth factor, have therefore been attractive therapeutic targets in CLL and many clinical trials were established in the past years. However, the results of these trials reveal that anti-angiogenic therapies alone are not as efficient as expected and should rather be used in combination with other treatments.

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