Significance of Marrow Angiogenesis Factors in Patients with Acute Myelogenous Leukemia.

Bone marrow (BM) neoangiogenesis plays an important role in the pathogenesis of acute myelogenous leukemia (AML). Paracrine exchange of growth factors among AML blasts, endothelial cells, and other marrow compartments is believed to contribute to the pathogenesis of AML. The vascular endothelial growth factor (VEGF) and the angiopoietin (ANG) family are the two major classes of growth factors associated with angiogenesis. In the present study, BM plasma from 52 AML patients and 20 normal donors were investigated. We measured the marrow concentrations of seven molecules associated with angiogenesis, VEGF, VEGF/PlGF, VEGF-C, VEGF-D, ANG-1, ANG-2, and Tie-2, by using enzyme-linked immunosorbent assay (ELISA). Compared to normal donors, the marrow levels of VEGF/PlGF, ANG-2, and Tie-2 were increased in patients with AML (p<0.005, <0.0001 and <0.0001, respectively). On the contrary, VEGF-C and ANG-1 levels were decreased in patients with AML (p<0.0001 and <0.0005, respectively). Although the values were not completely normalized, sequential study revealed that at complete remission (CR) period, VEGF/PlGF, ANG-2, and Tie-2 levels were decreased (p<0.005, <0.005 and =0.02, respectively), while VEGF-C increased (p=0.04). Kaplan-Meier survival curves showed that the subgroup of patients with lower Tie-2 level (29 ng/ml) had a longer median survival time than those with higher Tie-2 level (18.9 months versus 2.5 months, p<0.005). In addition, subgroups of patients with higher VEGF/PlGF level (1 pg/ml) and VEGF-D level (350 pg/ml) also had a longer median survival time than those with lower levels (20.8 months versus 7.2 months, p=0.03 and 18.9 months versus 3.4 months, p=0.03, respectively). Taken together, there were significant differences in VEGF/PlGF, VEGF-C, ANG-1, ANG-2, and Tie-2 expressions between AML patients and normal donors. Expressions of VEGF/PlGF, VEGF-D, and Tie-2 might be prognostic markers in AML patients.