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 language | English |
|---|---|
| Pages (from-to) | 1862-1871 |
| Number of pages | 10 |
| Journal | Stem Cells |
| Volume | 25 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2007 |
Fingerprint
Keywords
- Acute myeloid leukemia
- Angiopoietins
- Endothelial cells
- Tie-2
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Cell Biology
Cite this
Expression of tie-2 and other receptors for endothelial growth factors in acute myeloid leukemias is associated with monocytic features of leukemic blasts. / Riccioni, Roberta; Diverio, Daniela; Mariani, Gualtiero; Buffolino, Sonia; Riti, Viviana; Saulle, Ernestina; Petrucci, Eleonora; Cedrone, Michele; Lo-Coco, Francesco; Robin, Foà; Peschle, Cesare; Testa, Ugo.
In: Stem Cells, Vol. 25, No. 8, 08.2007, p. 1862-1871.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of tie-2 and other receptors for endothelial growth factors in acute myeloid leukemias is associated with monocytic features of leukemic blasts
AU - Riccioni, Roberta
AU - Diverio, Daniela
AU - Mariani, Gualtiero
AU - Buffolino, Sonia
AU - Riti, Viviana
AU - Saulle, Ernestina
AU - Petrucci, Eleonora
AU - Cedrone, Michele
AU - Lo-Coco, Francesco
AU - Robin, Foà
AU - Peschle, Cesare
AU - Testa, Ugo
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - Angiopoietins
KW - Endothelial cells
KW - Tie-2
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=34547916822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547916822&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2006-0700
DO - 10.1634/stemcells.2006-0700
M3 - Article
C2 - 17446561
AN - SCOPUS:34547916822
VL - 25
SP - 1862
EP - 1871
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 8
ER -