Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia.
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.
Schliemann
Christoph
C
Department of Medicine/Hematology and Oncology, and the IZKF Muenster, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany.
Bieker
Ralf
R
Padro
Teresa
T
Kessler
Torsten
T
Hintelmann
Heike
H
Buchner
Thomas
T
Berdel
Wolfgang E
WE
Mesters
Rolf M
RM
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*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D042787:Receptor, TIE-2