+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Antiangiogenic therapy in acute myelogenous leukemia: targeting of vascular endothelial growth factor and interleukin 8 as possible antileukemic strategies



Antiangiogenic therapy in acute myelogenous leukemia: targeting of vascular endothelial growth factor and interleukin 8 as possible antileukemic strategies



Current Cancer Drug Targets 5(4): 229-248



Acute myelogenous leukemia (AML) is an aggressive disorder with an overall disease-free survival of 40-50% even for the younger patients under 60 years of age who can receive the most intensive treatment. The median age at the time of diagnosis is 60-65 years, and the large majority of elderly patients usually receive less intensive chemotherapy or only supportive therapy due to the high treatment-related mortality when using intensive therapy for elderly individuals. Thus, there is a need for new therapeutic approaches to improve the treatment in younger patients and to make AML-directed therapy with acceptable toxicity possible in elderly individuals. Angiogenesis seems to be important both for leukemogenesis and susceptibility to intensive chemotherapy, and antiangiogenic strategies are therefore considered for the treatment of AML. The two proangiogenic mediators vascular endothelial growth factor (VEGF) and interleukin 8, (IL-8, also referred to as CXCL8) seem to be important in human AML: VEGF is released at increased levels due to interactions between AML cells and neighboring nonleukemic cells, whereas IL-8 is released at high levels by native human AML cells. Thus, VEGF as a therapeutic target in AML is suggested both by experimental and clinical observations, whereas IL-8 as a target is mainly suggested by experimental evidence. In the present review we describe and discuss (i) the angioregulatory network of soluble mediators in AML, including both the systemic levels and local release by native human AML cells; and (ii) various therapeutic approaches to target VEGF and IL-8. Although single angioregulatory mediators can be targeted, it should be emphasized that the final effect of soluble mediators on angioregulation is determined by a complex angioregulatory network that varies between AML patients, and the final effect of targeting single mediators may therefore differ between patient subsets.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 048274718

Download citation: RISBibTeXText

PMID: 15975045


Related references

Antiangiogenic Therapy in Acute Myelogenous Leukemia: Targeting of Vascular Endothelial Growth Factor and Interleukin 8 as Possible Antileukemic Strategies. Current Cancer Drug Targets 5(4): 229-248, 2005

Antiangiogenic therapy: targeting vascular endothelial growth factor and its receptors. Clinical Advances in Hematology and Oncology 1(1): 41-48, 2003

Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clinical Cancer Research 10(11): 3577-3585, 2004

Timed Sequential Therapy of Relapsed and Refractory Adult Acute Myelogenous Leukemia with the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab. Blood 100(11): Abstract No 744, 2002

Effects of vascular endothelial growth factor on acute myelogenous leukemia blasts. Journal of HematoTherapy and Stem Cell Research 10(1): 81-93, 2001

Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Research 59(21): 5412-5416, 1999

Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors. Molecular Cancer Therapeutics 5(12): 3105-3112, 2006

Effect of thalidomide and arsenic trioxide on the release of tumor necrosis factor-α and vascular endothelial growth factor from the KG-1a human acute myelogenous leukemia cell line. Oncology Letters 1(4): 663-667, 2010

Coculture of native human acute myelogenous leukemia blasts with fibroblasts and osteoblasts results in an increase of vascular endothelial growth factor levels. European Journal of Haematology 74(1): 24-34, 2005

Antiangiogenic agents targeting vascular endothelial growth factor and its receptors in clinical development. Expert Opinion on Investigational Drugs 11(10): 1447-1465, 2002

Participation of the cytokines interleukin 6, tumor necrosis factor-alpha, and interleukin 1-beta secreted by acute myelogenous leukemia blasts in autocrine and paracrine leukemia growth control. Journal of Clinical Investigation 84(2): 451-457, 1989

Anti-Vascular Endothelial Growth Factor Targeting by Curcumin and Thalidomide in Acute Myeloid Leukemia Cells. Asian Pacific Journal of Cancer Prevention 18(11): 3055-3061, 2017

Rational Design of Antiangiogenic Helical Oligopeptides Targeting the Vascular Endothelial Growth Factor Receptors. Frontiers in Chemistry 7: 170, 2019

Vascular endothelial growth factor as a target for antiangiogenic therapy. Journal of Clinical Oncology 18(21 Suppl): 45s-46s, 2000

New antiangiogenic strategies beyond inhibition of vascular endothelial growth factor with special focus on axon guidance molecules. Oncology 86(1): 46-52, 2014