title: Angiogenic factors may have a different prognostic role in adult acute lymphoblastic leukemia.
abstract: Angiogenesis plays an important role in solid tumors and hematologic malignancies. The prognostic significance of angiogenic factors in adult acute lymphoblastic leukemia (ALL) remains ambiguous. We therefore analyzed the impact of angiogenic factor levels on overall survival of newly diagnosed adult ALL patients. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-1 receptor alpha (IL-1Ralpha), IL-6, IL-8, VEGF receptors VEGFR1 and VEGFR2, and thrombopoietin (TPO) were measured in plasma samples of 95 patients by enzyme-linked immunosorbent assay (ELISA). In a univariate Cox proportional hazards model, higher levels of IL-1Ralpha, IL-8, VEGFR1, and VEGFR2 were predictive of poor survival. In contrast, higher levels of VEGF were predictive of longer survival, and higher levels of bFGF suggested a similar trend (P = .09). The multivariate model simultaneously included VEGF (relative risk [RR] for death, 8.01; P = .001 for levels less than or equal to 19.5 pg/mL), IL-1Ralpha (RR, 5.12; P = .007 for levels greater than 373 pg/mL), and VEGFR2 (RR, 4.01; P = .04 for levels greater than 8222 pg/mL) as independent factors for survival. Of interest is the association of high levels of VEGF with good prognosis and higher levels of VEGF receptors with poor outcome. These data reflect the complexity by which angiogenic factors may affect the clinical behavior of patients with ALL, and this complexity should be considered in any therapeutic strategy incorporating antiangiogenic agents.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Susan
authors.initials: S
authors.lastname: O'brien
authors.forename: Iman
authors.initials: I
authors.lastname: Jilani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi-Kashani
authors.forename: Christine
authors.initials: C
authors.lastname: Aguilar
authors.forename: Amanda
authors.initials: A
authors.lastname: Dey
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000097:blood*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D017472:Receptors, Interleukin-1 / Q000097:blood; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2