Elevated Serum Level of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Correlates with Stage of Chronic Lymphocytic Leukemia and Resistance to Treatment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4172-4172
Author(s):  
Bulat Bakirov ◽  
Anastasiya Sgibneva ◽  
Akhat Bakirov
Keyword(s):  
Growth Factor ◽  
High Risk ◽  
Serum Level ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
High Risk Disease ◽  
Endothelial Growth Factor

Abstract Background: B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in western world with an incidence of 3,36/100,000 in European males. It is characterized by a clonal growth of long lived, slowly proliferating mature B lymphoid cells in the bone marrow (BM), peripheral blood (PB), and lymphoid tissues. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Angiogenesis may have a role in a pathophysiology of leukemias and antiangiogenesis therapy could have an anticancer effect. Aim: analyze the clinical significance of serum levels of angiogenic factors and how it’s correlate with clinical stage and survival in patients with B-CLL Methods: the enzyme-linked immunosorbent assays (ELISAs) for VEGF and bFGF were performed in 78 CLL patients and 29 healthy person as a control group. The patients was divided on low-risk disease (44 patients) and high-risk disease (34 patients). Results: VEGF and bFGF serum levels were significantly increased in patient with high-risk disease, the median serum VEGF level was 185.66 pg/ml, compared with 72.67 pg/ml in patient with a low-risk and in control, it was 48.62 pg/ml. The difference in the VEGF levels was significant for the comparison between low- and high-risk disease (p<0.001). VEGF levels correlate with high white blood cell/lymphocyte counts, short period of time to begin treatment, disease progression, lymphocyte doubling time and worse answer to chemotherapy. No significant increase was found in bFGF serum level between low- and high-risk disease (34.06 pg/ml and 35.84 pg/ml, respectevely), but between patient and control group it was differences in serum level of bFGF (34.85 pg/ml and 7.77 pg/ml, respectively) (p<0.001). Conclusion: as we found, serum levels of bFGF and VEGF were significantly higher in the patients with B-CLL than in controls. High serum level of VEGF and bFGF associated with poor prognosis and worse answer on treatment. In summary, our data suggest that angiogenic factors play a significant role in the leukemic process and may suggest novel therapeutic approaches in B-CLL.

Serum Levels of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4387-4387
Author(s):  
Izabela Palgan ◽  
Mariusz Wysocki ◽  
Krzysztof Palgan ◽  
Robert Debski ◽  
Grazyna Odrowaz-Sypniewska ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Control Group ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Fibroblast Growth ◽  
Childhood All ◽  
Endothelial Growth Factor

Abstract Angiogenesis is a process of blood vessel formation from the preexisting capillaries. It plays an essential role of growth and development of cancer. The aim of this study was to evaluate serum levels of the most important angiogenic stimulators, Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in children with acute lymphoblastic leukemia (ALL) and their relation to clinical manifestations of the disease, and in healthy controls. Although VEGF and bFGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in hematopoietic malignancies and solid tumors, experience in childhood ALL has been limited. Patients and methods: 46 children with ALL (24 male, 22 female) aged 2-18 years (median 8 years) at the time of diagnosis and in remission and 70 healthy children (31 male, 39 female). For the quantitative determination of human VEGF and bFGF, the Quantikine (R&D Systems, Minneapolis, MN, USA), a solid phase enzyme-linked immunosorbent assay method was used. Elevated VEGF and bFGF were defined as being higher than the 95 percentile value in control group. Results: The range of VEGF serum levels in healthy controls was 24.73–467.7 pg/ml (median 168.9 pg/ml), 95 percentile was 431.85 pg/ml and the range of bFGF serum levels was 0–10.8 pg/ml (median 2.9 pg/ml), 95 percentile was 6.95 pg/ml. In children with ALL, the range of VEGF serum levels at the time of diagnosis was 0–532.3 pg/ml (median 91.18 pg/ml), and bFGF 0–64.48 pg/ml (median 5.11 pg/ml). In children in remission, the range of serum levels of VEGF was 53.15–962.67 pg/ml (median 209.73 pg/ml), and bFGF 0–32.5 pg/ml (median 5.98 pg/ml). The median level of VEGF at diagnosis was lower than those of the control group (p=0.006), and higher in remission, when compared to values obtained in children on diagnosis and in the control group (p=0.0005; p=0.01). Elevated level of VEGF was observed in 8.7% children at the time of diagnosis and in 24.4% of patients in remission. The median levels of bFGF at diagnosis and in remission were significantly higher than those in control group with 40% of children having elevated levels. A positive correlation between VEGF serum concentration and platelet number, and negative correlation between VEGF serum levels and WBC were observed, with no other correlations between growth factors (VEGF, bFGF) and age, type of lymphoblasts (FAB), risk group, and drug resistance. Conclusion: These results suggest that bFGF more than VEGF can play an important role in childhood ALL. The serum levels of angiogenic factors may be related to the activity of the disease, while both growth factors can possibly be a target of anti-angiogenic therapy.

Angiogenic Cytokines: Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Levels in Serum of Children with Hematopoietic Malignancies and Solid Tumors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3905-3905
Author(s):  
Izabela Palgan ◽  
Mariusz Wysocki ◽  
Krzysztof Palgan ◽  
Robert Debski ◽  
Jan Styczynski
Keyword(s):  
Growth Factor ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Serum Levels ◽  
Control Group ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Fibroblast Growth ◽  
Hematopoietic Malignancies ◽  
Endothelial Growth Factor

Abstract Angiogenesis is a process of blood vessel formation from the preexisting capillaries. It plays an essential role of growth and development of cancer. The most important angiogenic stimulators are Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF). The aim of the study was to evaluate the serum levels of VEGF and bFGF in children with solid tumors, hematological malignancies and in healthy controls. Patients: 110 children (33 with solid tumors and 77 with hematological malignancies, including 46 with acute lymphoblastic leukemia and 17 with acute myeloblastic leukemia) (56 male and 54 female) aged 2–18 years (median 8.5 years) and 70 healthy controls (31 male and 39 female) aged 3–18 years (median 13 years). For the quantitative determination the Quantikine VEGF and bFGF immunoassay, a solid-phase enzyme-linked immunosorbent assay method was used. Elevated VEGF and bFGF were defined as being higher than the 95 percentile value in control group. Results: At the time of diagnosis the range of VEGF serum levels in all cancer patiens was 0–2691.3 pg/ml, and in remission 6.08–967.67 pg/ml; while the range of bFGF at diagnosis was 0–64.48 pg/ml, and in remission 0–32.52 pg/ml. In all children with cancer, serum levels of VEGF and bFGF were significantly more often elevated than in healthy controls (p<0.004; p<0.0005). At diagnosis, almost 12% patients had simultaneously elevated serum levels of VEGF and bFGF. Among patients with solid tumors at the time of diagnosis, elevated levels of VEGF and bFGF was observed in 42% and 60%, respectively. There were no differences between serum levels of these factors in patients in remission and in control group. In patients with progression, serum levels of VEGF and bFGF were higher, when compared to levels of these factors at diagnosis. The range of serum levels of VEGF in children with solid tumors at the time of diagnosis was 85.96–2691.3 pg/ml (median 365.48 pg/ml), and in remission 6.08–787.16 pg/ml (median 204.1 pg/ml). The median level of VEGF at diagnosis in children with hematopoietic malignancies (range 0–1869.6 pg/ml, median 111.6 pg/ml) was lower than in children with solid tumors (p<0.0005). In children with acute leukemias at diagnosis, serum levels of VEGF were significantly lower than in children with lymphomas (p<0.0003) and in controls (p<0.05). These results suggest that evaluation of serum levels of VEGF and bFGF can be helpful for monitoring activity of cancer, particularly in solid tumors and in the future can be a target of anti-angiogenic therapy.

scholarly journals Plasma Concentrations of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Lymphoproliferative Disorders

2005 ◽  
Vol 48 (1) ◽  
pp. 57-58 ◽  
Author(s):  
Lukáš Smolej ◽  
Ctirad Andrýs ◽  
Vladimír Maisnar ◽  
Luděk Pour ◽  
Jaroslav Malý
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Endothelial Growth Factor

Angiogenesis plays a major role in the development and progression of haematological malignancies. In our study we measured plasma concentrations of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) using comercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 37 patients with lymphoid malignancies and 20 healthy donors. We found a statistically significant increase in bFGF concentrations in patients with B-cell chronic lymphocytic leukemia (B-CLL, n=18) compared to the control group (median 118.8 vs. 9.3 pg/ml, p<0.001). However, we didn’t find any significant difference in VEGF concentrations between B-CLL patients and the control group. There was also no significant increase in bFGF or VEGF in patients with multiple myeloma (n=7) and non-Hodgkin’s lymphoma (n=12). Our pilot study shows that measurement of angiogenic activators in plasma is a feasible and reproducible method of angiogenesis assessment. Larger studies are needed for correlation between serum and plasma concentrations and detailed statistical evaluation including the impact on patients’ survival.

scholarly journals Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1056-1063 ◽  
Author(s):  
T Menzel ◽  
Z Rahman ◽  
E Calleja ◽  
K White ◽  
EL Wilson ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Lymphocytic Leukemia ◽  
Potential Contribution ◽  
Fibroblast Growth ◽  
High Risk Disease ◽  
Cellular Source

Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 10(5) cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with intermediate disease. In patients with low- risk disease, the median bFGF level was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x 10(5) cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.

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