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Acute Leukemias

The role of VEGF and a functional link between VEGF and p27Kip1 in acute myeloid leukemia

Leukemia volume 23, pages 251–261 (2009)Cite this article

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 p27Kip1 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 p27Kip1 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.

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Acknowledgements

We thank Elise Nilsson for the excellent technical assistant. This work was supported by the Swedish National Research Council, the Swedish Cancer Society, the Swedish Children Cancer Foundation, Gunnar Nilsson Cancer Foundation, MAS Cancer Fondation, Kunlig Fysiografisk Sällskapet in Lund, Crafoordska stiftelsen, and Malmö Hospital Foundation, the Lund University Medical Faculty grant and Government Public Health Grant (ALF) to JLP.

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Author notes

  1. B Wegiel

    Present address: 2Current address: Transplant Center, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,

  2. B Wegiel and J Ekberg: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Laboratory Medicine, Center for Molecular Pathology, Clinical Research Center, Lund University, University Hospital, Malmö, Sweden

    B Wegiel, J Ekberg, K M Talasila, S Jalili & J L Persson

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  1. B Wegiel
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Correspondence to J L Persson.

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Wegiel, B., Ekberg, J., Talasila, K. et al. The role of VEGF and a functional link between VEGF and p27Kip1 in acute myeloid leukemia. Leukemia 23, 251–261 (2009). https://doi.org/10.1038/leu.2008.300

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