Endothelial tip cell formation induced by chronic lymphocytic leukemia plasma (JAK2 positivity amplified this effect)

Abstract

A subset of specialized endothelial cells, called tip cells, which guide expanding capillaries toward gradients of vascular endothelial growth factor (VEGF), are responsible for growing of capillaries during angiogenesis. Certain evidence has suggested the involvement of angiogenesis in the pathophysiology of chronic lymphocytic leukemia. Nevertheless, the direct effect of chronic lymphocytic leukemia (CLL) plasma on tip cell formation is yet to be fully determined. We aimed to evaluate whether the endothelial cells are able to form tip cells in the presence of CLL plasma. Human umbilical vein endothelial cells were treated with CLL patient's plasmas. The expression of CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) levels were detected by flow cytometry, qPCR, and immunocytochemical staining techniques. We found that CD34-and VEGFR2positive cells were increased following direct exposure to CLL plasma. Nevertheless, the presence of a higher absolute lymphocyte count and/or Janus kinase (JAK2) mutation could amplify both CD34 and VEGFR2 expression in cell culture. Our findings may suggest CLL plasma as a potential source of growth factors, which might be responsible for tip cell development. Nevertheless, the JAK2 mutation may potentiate this effect.