Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia.

Abstract

BACKGROUND AND OBJECTIVES:

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.

DESIGN AND 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).

INTERPRETATION AND 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: Christoph Schliemann, Ralf Bieker, Teresa Padro, Torsten Kessler, Heike Hintelmann, Thomas Buchner, Wolfgang E Berdel, Rolf M Mesters
• Journal: Haematologica (Haematologica) Vol. 91 Issue 9 Pg. 1203-11 (Sep 2006) ISSN: 1592-8721 [Electronic] Italy
• PMID: 16956819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Angiopoietin-2
• Angiopoietins
• Receptor, TIE-2

Topics

• Acute Disease
• Angiopoietin-1 (genetics)
• Angiopoietin-2 (genetics)
• Angiopoietins (genetics)
• Bone Marrow (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia, Myeloid (genetics)
• Receptor, TIE-2 (genetics)