title: Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia.
abstract: OBJECTIVE
  Angiopoietin-1 (Ang-1) and its natural antagonist angiopoietin-2 (Ang-2), both ligands for the receptor tyrosine kinase Tie2, are known to play an essential role in normal and pathological angiogenesis.
  
  
  METHODS
  We investigated the expression of Ang-1, Ang-2 and Tie2 by immunohistochemical analyses in bone marrow biopsies of 64 adult patients with newly diagnosed acute myeloid leukemia (AML) and correlated angiogenic factor expression with clinicopathological variables and long-term survival.
  
  
  RESULTS
  Expression of Ang-2 was significantly higher in the bone marrow of AML patients than in 16 control patients. In contrast, the levels of Ang-1 expression in AML patients did not differ from those found in controls. Thus, we observed a reversal of the Ang-1 and Ang-2 expression balance in the neoplastic bone marrow. Furthermore, Tie2 was significantly overexpressed in leukemic blasts. Patients expressing high levels of Ang-2 had significantly longer overall survival than those with low Ang-2 levels (52.7 vs. 14.7 months). Multivariate analysis revealed that karyotype and Ang-2 expression were independent prognostic factors for overall survival (hazard ratio [CI]: 3.06 [1.39-6.70] and 0.31 [0.14-0.69], respectively).
  
  
  CONCLUSIONS
  These data provide evidence that the alteration of angiopoietin balance in favor of Ang-2 may play a critical role in the pathophysiology of AML. Furthermore, high pre-therapeutic levels of Ang-2 in the bone marrow indicate a favorable prognosis in AML patients treated with polychemotherapy, although the mechanism is not yet known.
authors.affiliation: Department of Medicine/Hematology and Oncology, and the IZKF Muenster, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schliemann
authors.forename: Ralf
authors.initials: R
authors.lastname: Bieker
authors.forename: Teresa
authors.initials: T
authors.lastname: Padro
authors.forename: Torsten
authors.initials: T
authors.lastname: Kessler
authors.forename: Heike
authors.initials: H
authors.lastname: Hintelmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Buchner
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Mesters
mesh_terms: D000208:Acute Disease; D042683:Angiopoietin-1 / Q000235:genetics; D042702:Angiopoietin-2 / Q000235:genetics; D042682:Angiopoietins / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D042787:Receptor, TIE-2 / Q000235:genetics*
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D042787:Receptor, TIE-2