title: Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia.
abstract: Angiogenesis plays an important role in solid tumors and hematologic malignancies. The angiopoietins act as essential regulators in this process. We investigated the impact of circulating angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble Tie2 (sTie2) on overall survival in patients with acute myeloid leukemia (AML). Ang-1, Ang-2 and sTie2 were measured in plasma samples from 68 AML patients and 11 controls using enzyme-linked immunosorbent assay. Circulating levels of Ang-2 and sTie2 (median (range): 1098.0 (361.4-4147.6) pg/ml and 3.40 (1.21-10.00) ng/ml, respectively) were significantly elevated in AML patients as compared to controls (307.9 (199.7-1225.0) pg/ml and 2.88 (1.71-3.29) ng/ml; P<0.001 and P=0.014). In a univariate Cox proportional hazards model, higher levels of Ang-2 and sTie2 were predictive of poor survival. In multivariate analyses, Ang-2 and cytogenetics proved to be independent prognostic factors, with a relative risk of 4.07 (95% confidence interval (CI) 1.88-8.81) and 2.70 (95% CI 1.25-5.81), respectively. The 3-year survival rate for AML patients with Ang-2 levels>/=1495.6 pg/ml was only 14.7% compared to 64.7% for those with Ang-2 levels<1495.6 pg/ml. These data provide evidence that circulating Ang-2 represents an independent prognostic factor in AML and may be used as a prognostic tool in the risk-adapted management of AML.
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schliemann
authors.forename: R
authors.initials: R
authors.lastname: Bieker
authors.forename: N
authors.initials: N
authors.lastname: Thoennissen
authors.forename: J
authors.initials: J
authors.lastname: Gerss
authors.forename: R
authors.initials: R
authors.lastname: Liersch
authors.forename: T
authors.initials: T
authors.lastname: Kessler
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.forename: R M
authors.initials: RM
authors.lastname: Mesters
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D042787:Receptor, TIE-2 / Q000097:blood; D012307:Risk Factors; D012995:Solubility
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D042787:Receptor, TIE-2