Leukemia Research 26 (2002) 399–402 Comparison between pediatric acute myeloid leukemia (AML) and adult AML in VEGF and KDR (VEGF-R2) protein levels Sima Jeha a , Franklin O. Smith b , Elihu Estey c , Yu Shen d , Diane Liu d , Taghi Manshouri e , Maher Albitar e,∗ a Departments of Pediatrics, University of Texas, M.D. Anderson Cancer Center, P.O. Box 072, 1515 Holcombe Boulevard, Houston, TX 77030, USA b Department of Pediatrics, Medicine, Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, School of Medicine, Indiana University, 1044 West Walnut Street, Indianapolis, IN 46202, USA c Departments of Leukemia, University of Texas, M.D. Anderson Cancer Center, P.O. Box 072, 1515 Holcombe Boulevard, Houston, TX 77030, USA d Departments of Biostatistics, University of Texas, M.D. Anderson Cancer Center, P.O. Box 072, 1515 Holcombe Boulevard, Houston, TX 77030, USA e Departments of Hematopathology, University of Texas, M.D. Anderson Cancer Center, P.O. Box 072, 1515 Holcombe Boulevard, Houston, TX 77030, USA Received 2 April 2001; accepted 13 August 2001 Abstract We reported previously that high levels of vascular endothelial growth factor (VEGF) were associated with shorter survival in adult acute myeloid leukemia (AML) patients. In this study, cellular VEGF and its receptor, VEGF-R2 (kinase domain receptor (KDR)), were analyzed in 45 pediatric AML patients using Western blot and solid-phase radioimmunoassay (RIA). Cellular VEGF levels were significantly lower in pediatric AML compared to adult AML patients. In contrast, there was no significant difference in VEGF-R2 levels between adult and pediatric AML. Higher VEGF and VEGF-R2 levels in pediatric AML patients correlated with higher white blood cell (WBC). Unlike in adults, VEGF and VEGF-R2 levels in pediatric AML patients did not correlate with survival. This data suggest that the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from that in adult AML. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: VEGF; KDR; AML 1. Introduction The role of angiogenesis in mediating solid tumor growth and metastasis has been extensively studied and several an- tiangiogenic agents are being tested in treating neoplasms in which neovascularization is a prominent component [1–6]. Perez-Atayde et al. demonstrated an increase in bone marrow microvascular density in pediatric patients with acute lymphocytic leukemia (ALL) [7], which led to an in- creased interest in studying the effect of neovascularization on leukemia proliferation. It has been established that adult hematopoietic neoplasms are dependent on angiogenesis to varying degrees [8,9]. Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen and a directly acting an- giogenic factor [10,11]. It binds to two endothelial cell tyrosine kinase receptors, the fms-like tyrosine kinase (flt), also known as VEGF-R1, and the kinase domain receptor (KDR), also called VEGF-R2 [12]. Increased serum and ∗ Corresponding author. Tel.: +1-713-794-1292; fax: +1-713-794-1800. E-mail address: malbitar@mdanderson.org (M. Albitar). cellular levels of VEGF has been associated with growth, dissemination, metastasis and poor outcome in solid tumors. We have demonstrated increased vascularity in all types of adult leukemias (except chronic lymphocytic leukemia) [8], and we and others have demonstrated the role that various angiogenic factors play in the biology and clinical behavior of these leukemias [9]. The role of angiogenesis, and in particular, of the VEGF pathway is not known in pediatric (P-AML). In this study, we examined the prognostic significance of cellular VEGF and VEGF-R2 levels in newly diagnosed P-AML and compared these levels to those seen in adult (A-AML). 2. Materials and methods 2.1. Patients and samples Pretreatment cellular VEGF concentrations were mea- sured in diagnostic bone marrow samples from 45 pediatric patients with de novo AML who were enrolled on the Children’s Cancer Group protocols 2941 and 2961, and 0145-2126/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0145-2126(01)00149-7