All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

“…4,29 Although a causal relationship remains to be established, it is thus possible that the observed inhibition of MMP-9 production might result from HF-elicited VEGF downregulation. Indeed, due to the fact that B-CLL cells express VEGF receptors functionally active in angiogenesis, 29,30 the hypothesis of an autocrine loop of VEGF has to be considered in B-CLL, 31 and moreover, an autocrine stimulation of VEGFR-2 has been described to induce MMP-9 expression as well as cell growth and migration in some leukaemia. 32 Furthermore, elevated MMP-9 levels are also produced in the plasma of adult T-cell leukemia (ATL) patients; they are closely related to high VEGF levels and are significantly associated with strong ATL cell infiltration, suggesting that MMP-9 and VEGF could cooperate in invasion processes.…”

Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1

“…It was reported that CLL cells not only are capable of producing VEGF, 6 but VEGFRs were also found to be expressed on the surface of leukemic cells. [7][8][9] These observations have led to the hypothesis that the apoptosis defect of CLL cells is partly mediated through an autocrine feedback loop involving VEGF. 8 Sorafenib (BAY43-9006; Nexavar) is an oral multikinase inhibitor approved for the treatment of patients with advanced renal cell carcinoma 10 and those with unresectable hepatocellular carcinoma.…”

Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line

“…8 In post-natal life, KDR is expressed in the hematopoietic system. Leukemic cells of the lymphoid and myeloid type may express KDR and produce VEGF, suggesting an autocrine loop in the control mechanisms of leukemia: [9][10][11][12][13] in particular, KDR stimulation promotes migration, inhibits apoptosis and moderately enhances cell growth. In this regard, it is not elucidated whether the increase in leukemic cell growth is in part mediated by a proliferative stimulus, besides the apoptosis inhibition.…”

“…22 The co-expression of Flt1 and KDR in hematopoietic precursors renders difficult the investigation of the specific functional role, as compared to that of Flt1. 8,10,11,20 Noteworthily, KDR also co-operates with Flt1 to promote not only HSC survival 20 but also endothelial cell proliferation. 25 The human TF1 cell line may represent a suitable model to study the specific effects of KDR on hematopoietic progenitors, without any interference by other VEGF receptors.…”

“…Furthermore, TF1 do not express Flt4 (VEGFR3), which is co-expressed with KDR in diverse leukemic cell types. 11,26 It must also be noted that the TF1 cell line has been extensively utilized as a useful model to shed light into the mechanisms underlying the survival, proliferation and differentiation of normal HPCs. Indeed, TF1 cells share the phenotype of normal HPCs (i.e., they express CD34 and c-kit) and are granulocyte macrophage-colonystimulating factor (GM-CSF) dependent.…”