Expression of tie-2 and other receptors for endothelial growth factors in acute myeloid leukemias is associated with monocytic features of leukemic blasts

Roberta Riccioni, Daniela Diverio, Gualtiero Mariani, Sonia Buffolino, Viviana Riti, Ernestina Saulle, Eleonora Petrucci, Michele Cedrone, Francesco Lo-Coco, Foà Robin, Cesare Peschle, Ugo Testa

Research output: Contribution to journalArticle

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 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 vascular endothelial growth factor receptor 1 (VEGF-R1), -R2, and -R3. Tie-2+ AMLs were characterized 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. Finally, the in vitro growth of Tie-2+ AMLs in endothelial culture medium supplemented with VEGF and angiopoietins resulted in their partial endothelial differentiation. These observations suggest that Tie-2+ AMLs pertain to a mixed monocytic/endothelial lineage, derived from the malignant transformation of the normal counterpart represented by monocytic cells expressing endothelial markers. The autocrine angiopoietin/Tie-2 axis may represent a promising therapeutic target to improve the outcome of patients with monocytic AML.

Original languageEnglish
Pages (from-to)1862-1871
Number of pages10
JournalStem Cells
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Acute myeloid leukemia
  • Angiopoietins
  • Endothelial cells
  • Tie-2
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cell Biology

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