Expression of angiopoietins and vascular endothelial growth factors and their clinical significance in acute myeloid leukemia

Angiogenic factors play an essential role in normal and pathologic angiogenesis, but their clinical role in acute myeloid leukemia (AML) remains unclear. We investigated the expression of Ang-1, Ang-2, Tie2, VEGF-A, and VEGF-C genes in bone marrow (BM) mononuclear cells by real-time quantitative PCR (RQ-PCR) in a cohort of 126 patients with newly diagnosed de novo AML and normal marrow donors. Here we show that high pre-treatment levels of Ang-2 in the BM indicate an unfavorable prognosis in AML. Only karyotype (hazard ratio 2.19, 95% CI 1.25–3.42, P = 0.005) and expression of Ang-2 (hazard ratio 2.05, 95% CI 1.20–3.52, P = 0.009), but not other angiogenic factors, were independent prognostic factors for overall survival by multivariate analysis. The prognostic significance of Ang-2 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Subgroup analysis showed that Ang-2 expression had prognostic impact on patients with low (but not high) Ang-1 or Tie2 levels, and on patients with high (but not low) VEGF-A or VEGF-C levels.