Effect of High VEGF-C mRNA Expression on Achievement of Complete Remission in Adult Acute Myeloid Leukemia

Although vascular endothelial growth factor-C (VEGF-C) is known to be expressed in acute myeloid leukemia (AML) blasts, the relevance of VEGF-C in the clinical setting remains to be fully explored. We examined the effect of VEGF-C on achievement of complete remission (CR) in adult de novo AML and immune cell population profiles according to VEGF-C mRNA expression. In comparison of VEGF-C expression between the no-CR and CR groups, the CR group showed a trend toward higher levels of plasma VEGF-C (P =.088), whereas mRNA expression of VEGF-C was downregulated (P =.008). Next, patients with continuous data for VEGF-C were divided into two groups (low vs. high) by a ROC curve analysis. The low- versus high-level groups for plasma VEGF-C (RR of 0.20, P =.030), mRNA expression of VEGF-C (RR of 18.75, P =.003), and the ratio of plasma level to mRNA expression (RR of 0.05, P =.007) were potential predictors of CR on univariate analysis. After adjusting for potential clinical factors including genetic group, multivariate analyses revealed that high VEGF-C mRNA expression was an independent risk factor for failure of induction chemotherapy. Furthermore, patients with high VEGF-C mRNA expression had a lower frequency of NKT and CD8⁺ cells and showed a trend for a lower frequency of NK cells. These results suggest that interruption of VEGF-C signaling might be a potential therapeutic target for antileukemic treatment in AML patients.