Article

[Expression of vascular endothelial growth factor and its receptors KDR and Flt1 in acute myeloid leukemia].

Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 06/2003; 24(5):249-52.
Source: PubMed

ABSTRACT To evaluate the expression of vascular endothelial growth factor (VEGF) and its receptors KDR and Flt1 in patients with acute myeloid leukemia (AML).
The expression of VEGF and its receptors mRNA was assayed by RT-PCR, the plasma of VEGF by ELISA.
In 13 AML cell lines, the expression of VEGF, KDR and Flt1 mRNA were found in 13 (100%), 7 (53.8%) and 12 (92.3%), respectively. There were 21 (65.6%), 1 (3.1%), and 17 (53.1%) of 31 (AML) patients bone marrow mononuclear cells (BMMNCs) expressing VEGF, KDR and Flt1 mRNA, respectively. None of BMMNCs from 3 normal donor and CD(34)(+) cells from 2 normal donor was found to express VEGF, KDR and Flt1 mRNA. The plasma level of VEGF of 39 patients (new diagnosed, relapsed and secondary-AML) before treatment was (135.3 +/- 87.9) ng/L which was significantly higher than that of 15 complete remission (CR) patients (80.6 +/- 36.9) ng/L and 12 normal donors (80.6 +/- 33.1) micro g/L (P = 0.028, 0.007). The plasma level of VEGF of 15 non-responsive patients was (188.2 +/- 118.6) ng/L after two cycles of chemotherapy which was higher than that of 20 CR patients [(104.2 +/- 30.9) ng/L] (P = 0.004).
VEGF and its receptors KDR and Flt1 mRNAs were expressed in BMMNCs of AML patients. The plasma level of VEGF directly affected the response to chemotherapy in AML patients.

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    Article: Nuclear expression of FLT1 and its ligand PGF in FUS-DDIT3 carrying myxoid liposarcomas suggests the existence of an intracrine signaling loop.
    Mattias K Andersson, Melker Göransson, Anita Olofsson, Carola Andersson, Pierre Aman
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    ABSTRACT: The FUS-DDIT3 fusion oncogene encodes an abnormal transcription factor that has a causative role in the development of myxoid/round-cell liposarcomas (MLS/RCLS). We have previously identified FLT1 (VEGFR1) as a candidate downstream target gene of FUS-DDIT3. The aim of this study was to investigate expression of FLT1 and its ligands in MLS cells. HT1080 human fibrosarcoma cells were transiently transfected with FUS-DDIT3-GFP variant constructs and FLT1 expression was measured by quantitative real-time PCR. In addition, FLT1, PGF, VEGFA and VEGFB expression was measured in MLS/RCLS cell lines, MLS/RCLS tumors and in normal adiopocytes. We analyzed nine cases of MLS/RCLS and one cell line xenografted in mice for FLT1 protein expression using immunohistochemistry. MLS/RCLS cell lines were also analyzed for FLT1 by immunofluorescence and western blot. MLS/RCLS cell lines were additionally treated with FLT1 tyrosine kinase inhibitors and assayed for alterations in proliferation rate. FLT1 expression was dramatically increased in transfected cells stably expressing FUS-DDIT3 and present at high levels in cell lines derived from MLS. The FLT1 protein showed a strong nuclear expression in cells of MLS tissue as well as in cultured MLS cells, which was confirmed by cellular fractionation. Tissue array analysis showed a nuclear expression of the FLT1 protein also in several other tumor and normal cell types including normal adipocytes. The FLT1 ligand coding gene PGF was highly expressed in cultured MLS cells compared to normal adipocytes while the other ligand genes VEGFA and VEGFB were expressed to lower levels. A more heterogeneous expression pattern of these genes were observed in tumor samples. No changes in proliferation rate of MLS cells were detected at concentrations for which the kinase inhibitors have shown specific inhibition of FLT1. Our results imply that FLT1 is induced as an indirect downstream effect of FUS-DDIT3 expression in MLS. This could be a consequence of the ability of FUS-DDIT3 to hijack parts of normal adipose tissue development and reprogram primary cells to a liposarcoma-like phenotype. The findings of nuclear FLT1 protein and expression of corresponding ligands in MLS and normal tissues may have implications for tissue homeostasis and tumor development through auto- or intracrine signaling.
    BMC Cancer 01/2010; 10:249. · 3.01 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

12 normal donors
 
13 AML cell lines
 
15 complete remission
 
15 non-responsive patients
 
2 normal donor
 
3 normal donor
 
39 patients
 
acute myeloid leukemia
 
AML
 
AML patients
 
cycles
 
Flt1 mRNA
 
Flt1 mRNAs
 
plasma
 
plasma level
 
receptors KDR
 
receptors mRNA
 
RT-PCR
 
secondary-AML
 
vascular endothelial growth factor