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

Barbara Wegiel, Jenny Ekberg, K M Talasila, S Jalili, J L Persson

Research output: Contribution to journalArticlepeer-review

27 Citations (SciVal)

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 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.
Original languageEnglish
Pages (from-to)251-261
JournalLeukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Volume2008
Issue numberNov 6.
DOIs
Publication statusPublished - 2009

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Stem Cell and Pancreas Developmental Biology (013212044), Division of Urological Cancers (013243420)

Subject classification (UKÄ)

  • Cancer and Oncology

Fingerprint

Dive into the research topics of 'The role of VEGF and a functional link between VEGF and p27(Kip1) in acute myeloid leukemia.'. Together they form a unique fingerprint.

Cite this