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

• Published in: Blood Vol. 116; no. 10; pp. 1747 - 1754
• Main Authors: de Jonge, Hendrik J.M., Valk, Peter J.M., Veeger, Nic J.G.M., ter Elst, Arja, den Boer, Monique L., Cloos, Jacqueline, Haas, Valérie de, van den Heuvel-Eibrink, Marry M., Kaspers, Gertjan J.L., Zwaan, Christian M., Kamps, Willem A., Löwenberg, Bob, de Bont, Eveline S.J.M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 09.09.2010; Americain Society of Hematology
• Subjects: Adolescent; Adult; Age Factors; Aged; Biological and medical sciences; Child; Child, Preschool; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Count; Medical sciences; Middle Aged; Multivariate Analysis; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Prognosis; Risk Factors; Vascular Endothelial Growth Factor C - genetics; Young Adult; Human; Pediatrics; Acute myelogenous leukemia; Prognosis; Hematology; Adult; Malignant hemopathy; Predictive factor; Child; Cancer; Gene expression profile
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-03-270991

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 long-term prognosis and provides prognostic information in addition to well-known prognostic factors.