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Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies.

Medinger M, Fischer N, Tzankov A - J Oncol (2010)

Bottom Line: Angiogenesis is essential for malignant tumor growth.The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2.The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

ABSTRACT
Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies.

No MeSH data available.


Related in: MedlinePlus

(a) Microvascular architecture in normal bone marrow highlighted by CD34; note single capillaries. (b) Increased microvessel density in acute myelogenous leukemia and in (c) myeloproliferative neoplasm; note dilated sinus and atypical megakaryocytes in the latter.
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fig2: (a) Microvascular architecture in normal bone marrow highlighted by CD34; note single capillaries. (b) Increased microvessel density in acute myelogenous leukemia and in (c) myeloproliferative neoplasm; note dilated sinus and atypical megakaryocytes in the latter.

Mentions: Leukemias have been ever since associated with angiogenesis since the AML cell line HL-60 was first used to clone the VEGF gene [40]. The first demonstration that leukemia progression might be accompanied by an increase of bone marrow vascularization was provided by Judah Folkman's group [41], who demonstrated that the bone marrow of acute lymphoblastic leukemia (ALL) patients had increased blood vessel content compared to normal counterparts. Detailed analysis of bone marrow sections from ALL patients led to the development of a model to illustrate their irregular, albeit abundant, bone marrow vasculature. Moreover, it was also shown that urine and peripheral blood samples from ALL patients contained elevated levels of proangiogenic growth factors, namely, basic fibroblast growth factor (bFGF) and VEGF, which correlated with the increase of bone marrow angiogenesis [41, 42]. These studies raised the question of whether the growth of other types of hemato-lymphoid malignancies is also accompanied by increased angiogenesis, while proving that the basic molecular/cellular mechanisms occurring during leukemia expansion might be similar to those seen in solid tumors. The existence of an “angiogenesis switch”, first proposed for solid tumors [43], was therefore suggested to apply to hemato-lymphoid malignancies as well. “Angiogenesis switch” in leukemia is documented by increased bone marrow MVD (Figures 2(a) and 2(b)), increased expression of HIF-1, multiple proangiogenic factors (VEGF, bFGF, angiopoietin-2), soluble VEGFR, and decreased expression of endogenous angiogenesis inhibitors, such as thrombospondin-1 [11, 12].


Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies.

Medinger M, Fischer N, Tzankov A - J Oncol (2010)

(a) Microvascular architecture in normal bone marrow highlighted by CD34; note single capillaries. (b) Increased microvessel density in acute myelogenous leukemia and in (c) myeloproliferative neoplasm; note dilated sinus and atypical megakaryocytes in the latter.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875768&req=5

fig2: (a) Microvascular architecture in normal bone marrow highlighted by CD34; note single capillaries. (b) Increased microvessel density in acute myelogenous leukemia and in (c) myeloproliferative neoplasm; note dilated sinus and atypical megakaryocytes in the latter.
Mentions: Leukemias have been ever since associated with angiogenesis since the AML cell line HL-60 was first used to clone the VEGF gene [40]. The first demonstration that leukemia progression might be accompanied by an increase of bone marrow vascularization was provided by Judah Folkman's group [41], who demonstrated that the bone marrow of acute lymphoblastic leukemia (ALL) patients had increased blood vessel content compared to normal counterparts. Detailed analysis of bone marrow sections from ALL patients led to the development of a model to illustrate their irregular, albeit abundant, bone marrow vasculature. Moreover, it was also shown that urine and peripheral blood samples from ALL patients contained elevated levels of proangiogenic growth factors, namely, basic fibroblast growth factor (bFGF) and VEGF, which correlated with the increase of bone marrow angiogenesis [41, 42]. These studies raised the question of whether the growth of other types of hemato-lymphoid malignancies is also accompanied by increased angiogenesis, while proving that the basic molecular/cellular mechanisms occurring during leukemia expansion might be similar to those seen in solid tumors. The existence of an “angiogenesis switch”, first proposed for solid tumors [43], was therefore suggested to apply to hemato-lymphoid malignancies as well. “Angiogenesis switch” in leukemia is documented by increased bone marrow MVD (Figures 2(a) and 2(b)), increased expression of HIF-1, multiple proangiogenic factors (VEGF, bFGF, angiopoietin-2), soluble VEGFR, and decreased expression of endogenous angiogenesis inhibitors, such as thrombospondin-1 [11, 12].

Bottom Line: Angiogenesis is essential for malignant tumor growth.The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2.The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

ABSTRACT
Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies.

No MeSH data available.


Related in: MedlinePlus