fig1

Figure 1. Angiogenesis mediators in CLL niches. In lymphoid tissues, CLL cells establish bidirectional interactions with immune and resident cells. Crosstalk with stromal cells induces an angiogenic switch in CLL cells. Conversely, CLL cells secrete the indicated angiogenic factors, which influence the behavior of immune and resident cells to favor angiogenesis. CLL cells are also able to recruit and induce a proangiogenic phenotype in immune cells by secreting soluble factors, such as GM/CSF (granulocyte-macrophage colony stimulating factor), CCL3 (C-C Motif Chemokine Ligand 3), CCL4 (C-C Motif Chemokine Ligand 4), and NAMPT (Nicotinamide phosphoribosyltransferase). Both CLL and stromal cells also release exosomes, whose cargo (proteins and miRNAs) allows neovascularization and angiogenesis. CLL: Chronic lymphocytic leukemia; PDGF: platelet-derived growth factor; VEGF: vascular endothelial growth factor; ANG2: angiopoietin-2; TSP-1: thrombospondin-1; MMP-9: matrix metalloproteinase-9; bFGF: basic fibroblast growth factor.