Lee Sung-Eun, Lee Ji Yoon, Han A-Reum, Hwang Hee-Sun, Min Woo-Sung, Kim Hee-Je
Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Biomedical Laboratory Science, College of Health Sciences, Sangji University, Wonju, Korea.
Transl Oncol. 2018 Jun;11(3):567-574. doi: 10.1016/j.tranon.2018.02.018. Epub 2018 Mar 12.
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.
尽管已知血管内皮生长因子C（VEGF-C）在急性髓系白血病（AML）原始细胞中表达，但VEGF-C在临床环境中的相关性仍有待充分探索。我们根据VEGF-C mRNA表达情况，研究了VEGF-C对成人初发AML完全缓解（CR）达成情况及免疫细胞群体谱的影响。在比较未缓解组和缓解组之间的VEGF-C表达时，缓解组血浆VEGF-C水平有升高趋势（P = 0.088），而VEGF-C的mRNA表达下调（P = 0.008）。接下来，通过ROC曲线分析将有VEGF-C连续数据的患者分为两组（低水平组与高水平组）。血浆VEGF-C的低水平组与高水平组（风险比为0.20，P = 0.030）、VEGF-C的mRNA表达（风险比为18.75，P = 0.003）以及血浆水平与mRNA表达的比值（风险比为0.05，P = 0.007）在单因素分析中是CR的潜在预测指标。在对包括基因分组在内的潜在临床因素进行校正后，多因素分析显示高VEGF-C mRNA表达是诱导化疗失败的独立危险因素。此外，VEGF-C mRNA表达高的患者NKT细胞和CD8细胞频率较低，NK细胞频率也有降低趋势。这些结果表明，阻断VEGF-C信号通路可能是AML患者抗白血病治疗的潜在靶点。
