[Dynamic observation of vascular endothelial growth factor (VEGF)/VEGF-receptors expression in acute leukemia].

ABSTRACT

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF)/VEGF-receptors and its relation to bone marrow angiogenesis in acute leukemia patients before and after chemotherapy. METHODS: Bone marrow biopsies from 122 cases with different stages of human acute leukemia were immunostained with anti-vascular endothelial growth factor, anti-fms-like tyrosine kinase (Flt-1) and anti- kinase-domain insert containing receptor (KDR) antibodies with envision two-step immunohistochemical staining method. RESULTS: The expression of VEGF and KDR protein in remission patients was 5.3 (3.3 - 9.0) and 2.0 (1.0 - 4.0) being significantly lower than newly diagnosed untreated patients 6.0 (3.3 - 12.0) and 5.3 (3.3 - 8.0) (P < 0.05, 0.01). However nonsignificant decrease was shown among non-remission patients. In relapsed patients the expression of VEGF and KDR was significantly increased as compared with that in newly diagnosed patients. Flt-1 staining levels were in the same range between the newly diagnosed untreated patients and control group (P > 0.05), but significantly increased in remission or relapse patients, being 3.3 (1.7 - 5.3) in the remission group and 3.3 (2.0 - 5.3) in the relapse group (P < 0.01). Expression of VEGF and KDR protein was significantly higher in patients with a high degree of bone marrow microvessel counts as compared with those with a low degree and the expression correlated well with microvessel counts (P < 0.01). There was a positive correlation of the percentage of bone marrow blasts with VEGF and KDR expression in AML patients (r = 0.429, 0.359; P = 0.005, 0.02), and with VEGF expression in ALL patients (r = 0.522; P = 0.03). CONCLUSION: VEGF and its two specific cellular receptors are expressed in both haematopoietic cells and endothelial cells. VEGF may be a autocrine factor and modulates the angiogenic reaction in bone marrow as a paracrine factor. VEGF and its cellular receptor KDR may constitute promising targets for antiangiogenic and antileukemic treatment strategies.