Increased angiogenesis and Fas-ligand expression are independent processes in acute myeloid leukemia

Abstract 

We evaluated the clinical significance of tumor angiogenesis and Fas-ligand (FasL) expression using parameters including the microvessel count (MVC), vascular endothelial growth factor (VEGF) level, and FasL expression in patients with acute myeloid leukemia (AML). Paraffin-embedded bone marrow (BM) sections from 43 AML patients at diagnosis, 20 patients after subsequent induction therapy, and 18 controls with non-invasive lymphoma were stained immunohistochemically for von Willebrand factor (vWF) and FasL. VEGF in BM mononuclear cells from 32 AML patients at diagnosis and 10 controls, including bone marrow transplantation donors, was assayed by an ELISA method. We found that the mean MVC, VEGF level, and FasL expression in AML patients at diagnosis were significantly higher than those of controls, with a significant correlation between the MVC and VEGF levels (r=0.43). However, there were no correlations between FasL expression and MVC or VEGF level. The mean MVC and FasL expression after induction therapy were lower than those evaluated at diagnosis, but were higher than those of controls. There was a correlation between the MVC and percentage of BM blasts (r=0.479), but no correlation between the MVC, VEGF level, or FasL expression and other hematologic or clinical variables. Our findings provide evidence of increased angiogenesis and tumor immune escape in AML, and both angiogenesis and tumor immune escape are independent processes in AML.

Keywords: Angiogenesis, Microvessel count, VEGF, Tumor immune escape, Fas-ligand, AML

Abbreviations: AML, acute myeloid leukemia, APL, acute promyelocytic leukemia, ara-C, cytarabine, ATRA, all-trans retinoic acid, BM, bone marrow, BMT, bone marrow transplantation, CML, chronic myeloid leukemia, CR, complete remission, DLI, donor lymphocyte infusion, FAB, French–American–British, FasL, Fas-ligand, IDA, idarubicin, MDS, myelodysplastic syndrome, NK, natural killer, MNC, mononuclear cell, MVC, microvessel count, MVD, microvessel density, SD, standard deviation, VEGF, vascular endothelial growth factor, vWF, von Willebrand factor