Does Serum Soluble Vascular Endothelial Growth Factor Levels Have Different Importance in Pediatric Acute Leukemia and Malignant Lymphoma Patients?

Abstract

Vascular endothelial growth factor (VEGF) seems to play a central role in angiogenesis-lymphangiogenesis in hematological malignancies. There are limited data related to childhood hematologic malignancies. The aim of the study was to evaluate soluble VEGF (sVEGF) levels in children with acute leukemia and malignant lymphoma (ML) at diagnosis and in remission. The levels of serum sVEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 20 children with acute leukemia, 33 children with different histopathological subtypes of ML, and 20 healthy controls. The levels of sVEGF at diagnosis (range 2 -1040 pg/mL; median 52 pg/mL) was significantly lower than in remission (range 136 -1960 pg/mL; median 630 pg/mL) in acute myeloid leukemia (AML) group (P = .018). The sVEGF levels at diagnosis (range: 2 -640 pg/mL; median 89 pg/mL) was significantly lower compared to remission values (range: 116 -1960 pg/mL; median 136 pg/mL) in patients with acute lymphoblastic leukemia (ALL) (P = .002). In ML group, including Burkitt's lymphoma (BL), T-cell non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL), sVEGF levels at diagnosis were higher than remission levels, but there was no statistically significant difference (P >.05). On the other hand, there were significant difference between levels in active disease and control group, ie, BL versus control, T-cell NHL versus control, and HL versus control (P = .008, P = .043, P = .007, respectively). The authors noticed that sVEGF levels showed distinct behavioral pattern in different childhood malignancies at diagnosis and in remission. In acute leukemia and ML patients, VEGF acts through different pathophysiological mechanisms, in both bone marrow (BM) angiogenesis and lymphoid tissue lymphangiogenesis.

Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome

“…Its expression is associated with proliferation of neoplastic cells, their invasion and metastasis [ 24 ] VEGF may also play some role in pathogenesis of leukemia, since deregulation of VEGF expression and signaling pathways are observed in ALL [ 25 ]. Our data confirms studies by Kalra et al [ 26 ] and Dincaslan et al [ 27 ], demonstrating that untreated children with ALL have significantly lower VEGF concentration than controls and that, at the end of the induction therapy, VEGF increases to levels similar to controls [ 26 , 27 ]. Hence, we confirm also the hypothesis that since VEGF is expressed in normal hematopoietic cells, the renewal of normal hematopoiesis in the course of therapy may explain the increase in VEGF levels and be a predictor of good response to the chemotherapy.…”

Lymphoma: Immune Evasion Strategies

“…Vascular endothelial growth factor (VEGF) is also highly expressed by malignant lymphoma cells, correlating with disease progression and a negative response to therapy [ 131 , 132 , 133 ]. Circulating serum levels of VEGF are also elevated in lymphoma patients and a predictor of poor prognosis [ 134 , 135 , 136 ]. Mouse models demonstrate that engraftment of NHL directly correlates with tumor VEGF production, and targeting the VEGF pathway with neutralizing antibodies results in inhibition of tumor growth [ 137 , 138 ].…”

Vascular Endothelial Growth Factor Levels in Childhood Acute Lymphoblastic and Myeloblastic Leukemia

“…They concluded that there was a relation between VEGF levels and disease activation. But recent pediatric study is inconclusive about the same point that the VEGF levels of pediatric leukemia patients at diagnosis were lower than remissions by measuring serum soluble VEGF with Elisa [24]. Pruneri et al [22] have found that micro vessel density of MDS patients were lower than AML patients' were, but higher than controls.…”

“…Adult studies reveal more trust on VEGF and its prognostic value although studies on children are not [24]. Also there is a different method as PCR, Elisa, and Histopathology that may result in variations in the disease prognosis analyses.…”