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


CONCLUSIONS
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.
Wang
Chen
C
Deparmant of Leukemia Research, Shanghai Institute of Hematology, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China. pattywang@tom.com
Chen
Fang-Yuan
FY
Zhu
Jian-Shan
JS
Xu
Yan-Ping
YP
Han
Jie-Ying
JY
Ouyang
Ren-Rong
RR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2