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The role of VEGF and a functional link between VEGF and p27(Kip1) in acute myeloid leukemia.

Wegiel, Barbara LU ; Ekberg, Jenny LU ; Talasila, K M; Jalili, S and Persson, J L (2009) In Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2008(Nov 6.). p.251-261
Abstract
Alterations in the expression and signalling pathways of vascular endothelial growth factor (VEGF) have been linked to the clinical features and pathogenesis of hematologic malignancies. In this study, we showed that VEGF protein expression was statistically significantly higher in the leukemic blasts than in the normal hematopoietic counterparts. A statistically significant correlation between expression of VEGF and p27(Kip1) was observed in bone marrows from 42 patients with acute myeloid leukemia (P<0.001). We further demonstrated that forced VEGF overexpression or autocrine VEGF stimulation of VEGFR-2 triggers proliferation and migration/invasion of U-937 leukemic cells, thereby inducing a more invasive tumor phenotype. U-937 cells... (More)
Alterations in the expression and signalling pathways of vascular endothelial growth factor (VEGF) have been linked to the clinical features and pathogenesis of hematologic malignancies. In this study, we showed that VEGF protein expression was statistically significantly higher in the leukemic blasts than in the normal hematopoietic counterparts. A statistically significant correlation between expression of VEGF and p27(Kip1) was observed in bone marrows from 42 patients with acute myeloid leukemia (P<0.001). We further demonstrated that forced VEGF overexpression or autocrine VEGF stimulation of VEGFR-2 triggers proliferation and migration/invasion of U-937 leukemic cells, thereby inducing a more invasive tumor phenotype. U-937 cells overexpressing VEGF were resistant to all-trans-retinoic acid-(ATRA) or camptothecin-induced apoptosis. Finally, we showed that increased p27(Kip1) expression enhanced the ability of VEGF and VEGFR-2 to promote the migration of U-937 cells. Taken together, our results suggest that elevated level of VEGF may contribute to the adverse patient outcome by promoting cell growth, survival and migration of leukemic cells and by reducing the sensitivity of leukemic cells to therapeutic agents-induced apoptosis.Leukemia advance online publication, 6 November 2008; doi:10.1038/leu.2008.300. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
volume
2008
issue
Nov 6.
pages
251 - 261
publisher
Nature Publishing Group
external identifiers
  • wos:000263312300005
  • pmid:18987662
  • scopus:60149100926
ISSN
1476-5551
DOI
10.1038/leu.2008.300
language
English
LU publication?
yes
id
be701e9c-7ea4-4b21-a06a-29207f9c8497 (old id 1271791)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18987662?dopt=Abstract
date added to LUP
2008-12-03 12:34:34
date last changed
2017-01-15 04:25:40
@article{be701e9c-7ea4-4b21-a06a-29207f9c8497,
  abstract     = {Alterations in the expression and signalling pathways of vascular endothelial growth factor (VEGF) have been linked to the clinical features and pathogenesis of hematologic malignancies. In this study, we showed that VEGF protein expression was statistically significantly higher in the leukemic blasts than in the normal hematopoietic counterparts. A statistically significant correlation between expression of VEGF and p27(Kip1) was observed in bone marrows from 42 patients with acute myeloid leukemia (P&lt;0.001). We further demonstrated that forced VEGF overexpression or autocrine VEGF stimulation of VEGFR-2 triggers proliferation and migration/invasion of U-937 leukemic cells, thereby inducing a more invasive tumor phenotype. U-937 cells overexpressing VEGF were resistant to all-trans-retinoic acid-(ATRA) or camptothecin-induced apoptosis. Finally, we showed that increased p27(Kip1) expression enhanced the ability of VEGF and VEGFR-2 to promote the migration of U-937 cells. Taken together, our results suggest that elevated level of VEGF may contribute to the adverse patient outcome by promoting cell growth, survival and migration of leukemic cells and by reducing the sensitivity of leukemic cells to therapeutic agents-induced apoptosis.Leukemia advance online publication, 6 November 2008; doi:10.1038/leu.2008.300.},
  author       = {Wegiel, Barbara and Ekberg, Jenny and Talasila, K M and Jalili, S and Persson, J L},
  issn         = {1476-5551},
  language     = {eng},
  number       = {Nov 6.},
  pages        = {251--261},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K},
  title        = {The role of VEGF and a functional link between VEGF and p27(Kip1) in acute myeloid leukemia.},
  url          = {http://dx.doi.org/10.1038/leu.2008.300},
  volume       = {2008},
  year         = {2009},
}