Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads to cell survival mediated though vascular endothelial growth factor expression.

Lysophosphatidic acid (LPA) protects chronic lymphocytic leukemia (CLL) cells from apoptosis. Vascular endothelial growth factor (VEGF) also protects CLL cells against apoptosis. The mechanism for LPA protection against apoptosis in CLL cells is unknown. Herein, we show CLL cells express LPA receptors LPA(1-5) but in normal B cells, LPA(1) was rarely expressed and LPA(3,) LPA(4,) and LPA(6) were undetectable whereas the other LPA receptors were expressed. LPA plasma levels are similar in patients with CLL compared to healthy controls. In contrast, plasma levels of VEGF are elevated in patients with CLL compared to healthy controls and LPA treatment induced VEGF secretion in CLL cells. CLL cells also express VEGF receptors and LPA protection against Flu induced apoptosis is blocked by inhibition of VEGF receptor activation. These results indicate that LPA protects CLL cells from apoptosis through higher expression of LPA receptors and autocrine production of VEGF.