Expression of Tie-2 and Other Receptors for Endothelial Growth Factors in Acute Myeloid Leukemias Is Associated with Monocytic Features of Leukemic Blasts

¹ Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, ROME, ITALY
² Department of Cellular Biotechnologies and Hematology, University "La Sapienza", ROME, ITALY
³ Hematology Section, Ospedale San Giovanni, ROME, ITALY
⁴ Department of Biopathology, University Tor Vergata, ROME, ITALY

^* To whom correspondence should be addressed. E-mail: u.testa{at}iss.it.

	Abstract

We investigated the expression of Tie-2 in primary blasts from 111 patients with acute myeloid leukemia (AML) to evaluate a possible linkage between the expression of this receptor and the immunophenotypic and biologic properties of leukemic blasts. Tie-2 was expressed at moderate and high levels in 39 and 23 out of 111 AMLs, respectively. The analysis of the immunophenotype clearly showed that Tie-2 expression in AML was associated with monocytic features. Interestingly, Tie-2 expression on AML blasts was associated with concomitant expression of other receptors for endothelial growth factors, such as VEGF-R1, -R2 and -R3. Tie-2⁺ AMLs were characterised by high blast cell counts at diagnosis, a high frequency of Flt3 mutations and increased Flt3 expression. The survival of Tie-2⁺ AMLs is sustained through an autocrine pattern involving angiopoietin-1 and Tie-2, as suggested by experiments showing induction of apoptosis in Tie-2⁺ AMLs by agents preventing the binding of angiopoietins to Tie-2.