High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia.. Homo sapiens

High VEGFC mRNA expression of AML blasts is related to increased in vitro and in vivo drug resistance. The prognostic significance of VEGFC on long-term outcome and its associated gene expression profiles remain to be defined. We studied the effect of VEGFC on treatment outcome and investigated gene expression profiles associated with VEGFC using microarray data of 525 adult and 100 pediatric AML patients. High VEGFC expression appeared strongly associated with reduced complete remission rate, reduced overall and event-free survival (OS and EFS) in adult AML. Multivariable analysis established high VEGFC as prognostic indicator independent of cytogenetic risk, FLT3-ITD, NPM1, CEBPA, age and WBC. Also in pediatric AML high VEGFC was related to reduced OS. A unique series of differentially expressed genes was identified that distinguished AML with high VEGFC from AML with low VEGFC, i.e., 331 upregulated genes (representative of proliferation, VEGF-receptor activity, signal transduction) and 44 downregulated genes (e.g. related to apoptosis) consistent with a role in enhanced chemoresistance. In conclusion, high VEGFC predicts adverse long-term prognosis and provides prognostic information in addition to well-known prognostic factors. Overall design: 98 bone marrow and peripheral blood samples were collected at diagnosis and frozen. They were later thawed and hybridized to Affymetrix U133 Plus 2.0 arrays.

急性髓系白血病（AML）母细胞的血管内皮生长因子C（VEGFC）mRNA高表达与体外及体内药物耐药性增强相关。VEGFC对患者长期预后的预后价值及其相关基因表达谱仍有待阐明。本研究通过分析525例成人及100例儿童AML患者的微阵列数据，探讨了VEGFC对治疗结局的影响，并分析了与VEGFC相关的基因表达谱。在成人AML患者中，VEGFC高表达与完全缓解率降低、总生存期（OS）及无事件生存期（EFS）缩短显著相关。多变量分析显示，VEGFC高表达可作为独立于细胞遗传学风险、FLT3-ITD、NPM1、CEBPA、年龄及白细胞计数（WBC）的预后指标。在儿童AML患者中，VEGFC高表达同样与OS缩短相关。本研究鉴定出一组独特的差异表达基因，可区分VEGFC高表达与低表达的AML患者：其中331个上调基因（与细胞增殖、血管内皮生长因子受体活性及信号转导相关）及44个下调基因（例如与细胞凋亡相关），与增强化疗耐药的作用一致。综上，VEGFC高表达可预测不良长期预后，且可在已知预后因素之外提供额外的预后信息。实验整体设计：本研究收集了98例确诊时的骨髓及外周血样本并予以冷冻保存，后续解冻后与Affymetrix U133 Plus 2.0基因芯片进行杂交。