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Blood, 1 August 2004, Vol. 104, No. 3, pp. 788-794. Prepublished online as a Blood First Edition Paper on March 2, 2004; DOI 10.1182/blood-2003-08-2763. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2763v1 104/3/788    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, Y. K. Articles by Kay, N. E. Search for Related Content PubMed PubMed Citation Articles by Lee, Y. K. Articles by Kay, N. E. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG), in B-cell chronic lymphocytic leukemia Yean K. Lee, Nancy D. Bone, Ann K. Strege, Tait D. Shanafelt, Diane F. Jelinek, and Neil E. Kay From the Division of Hematology, Department of Medicine, Mayo Clinic; and Department of Immunology, Mayo Clinic, Rochester, MN. We recently reported that chronic lymphocytic leukemia (CLL) cells synthesize and release vascular endothelial growth factor (VEGF) under normoxic and hypoxic conditions. CLL B cells also express VEGF membrane receptors (VEGF-R1 and VEGF-R2), suggesting that they use VEGF as a survival factor. To assess the mechanism of apoptosis resistance related to VEGF, we determined the impact of VEGF on CLL B cells, and we studied the impact of epigallocatechin-3-gallate (EGCG), a known receptor tyrosine kinase (RTK) inhibitor, on VEGF receptor status and viability of CLL B cells. VEGF165 significantly increased apoptotic resistance of CLL B cells, and immunoblotting revealed that VEGF-R1 and VEGF-R2 are spontaneously phosphorylated on CLL B cells. EGCG significantly increased apoptosis/cell death in 8 of 10 CLL samples measured by annexin V/propidium iodide (PI) staining. The increase in annexin V/PI staining was accompanied by caspase-3 activation and poly–adenosine diphosphate ribose polymerase (PARP) cleavage at low concentrations of EGCG (3 µg/mL). Moreover, EGCG suppressed the proteins B-cell leukemia/lymphoma-2 protein (Bcl-2), X-linked inhibitor of apoptosis protein (XIAP), and myeloid cell leukemia-1 (Mcl-1) in CLL B cells. Finally, EGCG (3-25 µg/mL) suppressed VEGF-R1 and VEGF-R2 phosphorylation, albeit incompletely. Thus, these results suggest that VEGF signaling regulates survival signals in CLL cells and that interruption of this autocrine pathway results in caspase activation and subsequent leukemic cell death. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. K. Ghosh, T. D. Shanafelt, A. Cimmino, C. Taccioli, S. Volinia, C.-g. Liu, G. A. Calin, C. M. Croce, D. A. Chan, A. J. Giaccia, et al. Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells Blood, May 28, 2009; 113(22): 5568 - 5574. [Abstract] [Full Text] [PDF] J. Ruan, K. Hajjar, S. Rafii, and J. P. Leonard Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma Ann. Onc., March 1, 2009; 20(3): 413 - 424. [Abstract] [Full Text] [PDF] A. K. Ghosh, N. E. Kay, C. R. Secreto, and T. D. 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