High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia
High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia
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DOI：
10.1182/blood-2010-03-270991
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发表时间：
2010-09-09
期刊：
影响因子：
20.3
通讯作者：
de Bont, Eveline S. J. M.
中科院分区：
文献类型：
--
作者：
de Jonge, Hendrik J. M.;Valk, Peter J. M.;de Bont, Eveline S. J. M.
VEGFC mRNA在急性髓细胞白血病（AML）原始细胞中的高表达与体内外耐药性增加有关。VEGFC对长期预后的预后意义及其相关基因表达谱仍有待确定。我们研究了VEGFC对治疗结果的影响，并使用525名成人和100名儿童AML患者的微阵列数据研究了与VEGFC相关的基因表达谱。VEGFC高表达与成人AML的完全缓解率降低（P = 0.004）、总生存期和无事件生存期（OS和EFS）降低（分别为P = 0.002和P <0.001）密切相关。多变量分析确定高VEGFC为独立于细胞遗传学风险、FLT 3-ITD、NPM 1、CEBPA、年龄和白色血细胞计数的预后指标（OS P = 0.038; EFS P = 0.006）。此外，在儿童AML中，高VEGFC与OS降低相关（P = 0.041）。鉴定了一系列独特的差异表达基因，这些基因可将VEGFC高的AML与VEGFC低的AML区分开来，即331个上调基因（代表增殖、血管内皮生长因子受体活性、信号转导）和44个下调基因（例如，与细胞凋亡相关），这些基因与增强的化疗耐药性一致。总之，高VEGFC预测不良的长期预后，并提供预后信息，除了众所周知的预后因素。（血。2010; 116（10）：1747-1754）
High VEGFC mRNA expression of acute myeloid leukemia (AML) blasts is related to increased in vitro and in vivo drug resistance. Prognostic significance of VEGFC on long-term outcome and its associated gene expression profiles remain to be defined. We studied effect of VEGFC on treatment outcome and investigated gene expression profiles associated with VEGFC using microarray data of 525 adult and 100 pediatric patients with AML. High VEGFC expression appeared strongly associated with reduced complete remission rate (P = .004), reduced overall and event-free survival (OS and EFS) in adult AML (P = .002 and P < .001, respectively). Multivariable analysis established high VEGFC as prognostic indicator independent of cytogenetic risk, FLT3-ITD, NPM1, CEBPA, age, and white blood cell count (P = .038 for OS; P = .006 for EFS). Also, in pediatric AML high VEGFC was related to reduced OS (P = .041). A unique series of differentially expressed genes was identified that distinguished AML with high VEGFC from AML with low VEGFC, that is, 331 up-regulated genes (representative of proliferation, vascular endothelial growth factor receptor activity, signal transduction) and 44 down-regulated genes (eg, related to apoptosis) consistent with a role in enhanced chemoresistance. In conclusion, high VEGFC predicts adverse longterm prognosis and provides prognostic information in addition to well-known prognostic factors. (Blood. 2010; 116(10):1747-1754)