Possible Autocrine Mechanism of Placenta Growth Factor / Vascular Endothelial Growth Factor Receptor Type 1 in Acute Lymphoblastic Leukemia with Philadelphia Chromosome.

Abstract

The growth and/or survival of leukemia cells are affected by endothelial cell associated factors such as vascular endothelial growth factor (VEGF). Here, we studied the mRNA expression of VEGF and placenta growth factor (PLGF), a VEGF-related molecule, of acute lymphoblastic leukemia (ALL) cells (10 Philadelphia chromosome (Ph1) positive cases and 10 Ph1 negative cases) by real-time PCR. The expression of PLGF mRNA was significantly higher in Ph1 positive cases than Ph1 negative cases (p<0.05). The expression of VEGF mRNA was not different between Ph1 positive and negative cases. Then, recombinant PLGF was added to the culture of ALL cell lines: the growth of CRL1929 (Ph1 positive) was augmented by PLGF in a dose-dependent manner, while the growth of Nalm6 (Ph1 negative) was not affected by the addition of PLGF. Here, the growth enhancement effect of PLGF on CRL1929 was cancelled by the simultaneous addition of VEGF receptor type 1-Fc (VEGFR1-Fc), which binds to PLGF and abrogates the function. The growth enhancement effect was not cancelled by the simultaneous addition of VEGFR2-Fc, which binds to VEGF, but not to PLGF. Recombinant VEGF did not affect the growth of either cell line. Our data demonstrated that PLGF has a growth promoting effect on Ph1 positive ALL cells, and autocrine mechanism of PLGF-VEGFR1 might work in Ph1 positive ALL.