SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-07-2143. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2143v1 101/8/3174    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 Jones, D. T. Articles by Wickremasinghe, R. G. Search for Related Content PubMed PubMed Citation Articles by Jones, D. T. Articles by Wickremasinghe, R. G. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 3174-3180 NEOPLASIA Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis Dylan T. Jones, Kanagasabai Ganeshaguru, Robert J. Anderson, Trevor R. Jackson, K. Richard Bruckdorfer, Sylvia Y. Low, Lars Palmqvist, H. Grant Prentice, A. Victor Hoffbrand, Atul B. Mehta, and R. Gitendra Wickremasinghe From the Departments of Hematology and Biochemistry and Molecular Biology, Royal Free and University College Medical School, London, United Kingdom; and the Institute of Laboratory Medicine, Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden. Activation of the phosphatidylinositol 3- kinase/AKT pathway antagonizes apoptosis in diverse cellular systems. We previously showed that human plasma activated AKT and potently blocked the ability of chlorambucil or gamma radiation to induce apoptosis of B-chronic lymphocytic leukemia (CLL) cells. Here we report experiments that identify albumin as the major component of plasma that blocks CLL cell killing by chlorambucil or radiation. Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis. Both functions were restored by re-addition of albumin. The protective action of albumin as well as AKT activation was compromised by the binding of lipids. Fluorescence-activated cell sorter (FACScan) analysis demonstrated the uptake of fluoresceinated albumin by CLL cells. Accumulation of albumin in intracellular vesicles was also shown by confocal microscopy. Indirect inhibition of AKT activation by the phosphatidylinositol 3-kinase inhibitor LY294002 reversed the blockade of chlorambucil-induced killing by plasma albumin. The data suggest that activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis. Strategies designed to block albumin-induced antiapoptotic signaling may, therefore, be of value in enhancing cytotoxic drug action on CLL cells. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. Steele, A. G. Prentice, A. V. Hoffbrand, B. C. Yogashangary, S. M. Hart, M. W. Lowdell, E. R. Samuel, J. M. North, E. P. Nacheva, A. Chanalaris, et al. 2-phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells Blood, August 6, 2009; 114(6): 1217 - 1225. [Abstract] [Full Text] [PDF] R. G. Wickremasinghe Why is CLL refractory to bortezomib? Blood, November 1, 2008; 112(9): 3540 - 3541. [Full Text] [PDF] F.-T. Liu, S. G. Agrawal, Z. Movasaghi, P. B. Wyatt, I. U. Rehman, J. G. Gribben, A. C. Newland, and L. Jia Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib Blood, November 1, 2008; 112(9): 3835 - 3846. [Abstract] [Full Text] [PDF] A. J. Steele, A. G. Prentice, A. V. Hoffbrand, B. C. Yogashangary, S. M. Hart, E. P. Nacheva, J. D. Howard-Reeves, V. M. Duke, P. D. Kottaridis, K. Cwynarski, et al. p53-mediated apoptosis of CLL cells: evidence for a transcription-independent mechanism Blood, November 1, 2008; 112(9): 3827 - 3834. [Abstract] [Full Text] [PDF] M. Barragan, M. de Frias, D. Iglesias-Serret, C. Campas, E. Castano, A. F. Santidrian, L. Coll-Mulet, A. M. Cosialls, A. Domingo, G. Pons, et al. Regulation of Akt/PKB by phosphatidylinositol 3-kinase-dependent and -independent pathways in B-cell chronic lymphocytic leukemia cells: role of protein kinase C{beta} J. Leukoc. Biol., December 1, 2006; 80(6): 1473 - 1479. [Abstract] [Full Text] [PDF] M. Visser, S. B Kritchevsky, A. B Newman, B. H Goodpaster, F. A Tylavsky, M. C Nevitt, T. B Harris, and for the Health, Aging and Body Composition Study Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study Am. J. Clinical Nutrition, September 1, 2005; 82(3): 531 - 537. [Abstract] [Full Text] [PDF] A. Petlickovski, L. Laurenti, X. Li, S. Marietti, P. Chiusolo, S. Sica, G. Leone, and D. G. Efremov Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells Blood, June 15, 2005; 105(12): 4820 - 4827. [Abstract] [Full Text] [PDF] D. L. Kienle, C. Korz, B. Hosch, A. Benner, D. Mertens, A. Habermann, A. Krober, U. Jager, P. Lichter, H. Dohner, et al. Evidence for Distinct Pathomechanisms in Genetic Subgroups of Chronic Lymphocytic Leukemia Revealed by Quantitative Expression Analysis of Cell Cycle, Activation, and Apoptosis-Associated Genes J. Clin. Oncol., June 1, 2005; 23(16): 3780 - 3792. [Abstract] [Full Text] [PDF] A. J. Marks, M. S. Cooper, R. J. Anderson, K. H. Orchard, G. Hale, J. M. North, K. Ganeshaguru, A. J. Steele, A. B. Mehta, M. W. Lowdell, et al. Selective Apoptotic Killing of Malignant Hemopoietic Cells by Antibody-Targeted Delivery of an Amphipathic Peptide Cancer Res., March 15, 2005; 65(6): 2373 - 2377. [Abstract] [Full Text] [PDF] X. Hu, N. Haney, D. Kropp, A. F. Kabore, J. B. Johnston, and S. B. Gibson Lysophosphatidic Acid (LPA) Protects Primary Chronic Lymphocytic Leukemia Cells from Apoptosis through LPA Receptor Activation of the Anti-apoptotic Protein AKT/PKB J. Biol. Chem., March 11, 2005; 280(10): 9498 - 9508. [Abstract] [Full Text] [PDF] M. W. Graner, A. Likhacheva, J. Davis, A. Raymond, J. Brandenberger, A. Romanoski, S. Thompson, E. Akporiaye, and E. Katsanis Cargo from Tumor-Expressed Albumin Inhibits T-Cell Activation and Responses Cancer Res., November 1, 2004; 64(21): 8085 - 8092. [Abstract] [Full Text] [PDF] A. P. Mone, P. Huang, H. Pelicano, C. M. Cheney, J. M. Green, J. Y. Tso, A. J. Johnson, S. Jefferson, T. S. Lin, and J. C. Byrd Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells Blood, March 1, 2004; 103(5): 1846 - 1854. [Abstract] [Full Text] [PDF] D. T. Jones, E. Addison, J. M. North, M. W. Lowdell, A. V. Hoffbrand, A. B. Mehta, K. Ganeshaguru, N. I. Folarin, and R. G. Wickremasinghe Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs Blood, March 1, 2004; 103(5): 1855 - 1861. [Abstract] [Full Text] [PDF] N. W. C. J. van de Donk, D. Schotte, M. M. J. Kamphuis, A. M. W. van Marion, B. van Kessel, A. C. Bloem, and H. M. Lokhorst Protein Geranylgeranylation Is Critical for the Regulation of Survival and Proliferation of Lymphoma Tumor Cells Clin. Cancer Res., November 15, 2003; 9(15): 5735 - 5748. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020