Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Angiogenesis plays an important role in solid tumors and hematologic malignancies. The angiopoietins act as essential regulators in this process. We investigated the impact of circulating angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble Tie2 (sTie2) on overall survival in patients with acute myeloid leukemia (AML). Ang-1, Ang-2 and sTie2 were measured in plasma samples from 68 AML patients and 11 controls using enzyme-linked immunosorbent assay. Circulating levels of Ang-2 and sTie2 (median (range): 1098.0 (361.4-4147.6) pg/ml and 3.40 (1.21-10.00) ng/ml, respectively) were significantly elevated in AML patients as compared to controls (307.9 (199.7-1225.0) pg/ml and 2.88 (1.71-3.29) ng/ml; P<0.001 and P=0.014). In a univariate Cox proportional hazards model, higher levels of Ang-2 and sTie2 were predictive of poor survival. In multivariate analyses, Ang-2 and cytogenetics proved to be independent prognostic factors, with a relative risk of 4.07 (95% confidence interval (CI) 1.88-8.81) and 2.70 (95% CI 1.25-5.81), respectively. The 3-year survival rate for AML patients with Ang-2 levels>/=1495.6 pg/ml was only 14.7% compared to 64.7% for those with Ang-2 levels<1495.6 pg/ml. These data provide evidence that circulating Ang-2 represents an independent prognostic factor in AML and may be used as a prognostic tool in the risk-adapted management of AML.