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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-07-2143. This Article 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 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 Social Bookmarking                   What's this? Submitted July 18, 2002 Accepted December 1, 2002 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 R Bruckdorfer, Sylvia Y Low, Lars Palmqvist, H G Prentice, A V Hoffbrand, Atul B Mehta, and R G Wickremasinghe* Hematology, Royal Free and University College Medical School, London, United Kingdom Biochemistry and Molecular Biology, Royal Free and University College Medical School, London, United Kingdom Institute of Laboratory Medicine, Sahlgrenska University Hospital, Goteborg, Sweden * Corresponding author; email: r.wickremasinghe{at}rfc.ucl.ac.uk. 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 radiation to induce apoptosis of B-chronic lymphocytic leukemia (CLL) cells. Here we report experiments that identify albumin as the major component of plasma which blocks CLL cell killing by chlorambucil or radiation. Normal 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. 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 anti-apoptotic signaling may therefore be of value in enhancing cytotoxic drug action on CLL cells. 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? 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