SEARCH:   Advanced

Blood, 19 February 2009, Vol. 113, No. 8, pp. 1723-1729. Prepublished online as a Blood First Edition Paper on December 8, 2008; DOI 10.1182/blood-2008-02-137737. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-137737v1 113/8/1723    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 Levy, D. S Articles by Kumar, R. Search for Related Content PubMed PubMed Citation Articles by Levy, D. S Articles by Kumar, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 6, 2008 Accepted October 23, 2008 AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines Dana S Levy, Jason A Kahana, and Rakesh Kumar* Oncology Biology, GlaxoSmithKline, Collegeville, PA, United States * Corresponding author; email: rakesh.2.kumar{at}gsk.com. The PI3K/AKT signaling is activated in various hematological malignancies. We evaluated the effect of a novel, pan-AKT kinase inhibitor, GSK690693, on the proliferation of 112 cell lines representing different hematological neoplasia. Fifty five percent of all cell lines tested were sensitive to AKT inhibitor (EC50 < 1 µM), with acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma and Burkitt's lymphoma showing 89, 73 and 67% sensitivity to GSK690693, respectively. The anti-prolierative effect was selective for the malignant cells, as GSK690693 did not inhibit the proliferation of normal human CD4+ peripheral T lymphocytes as well as mouse thymocytes. Phosphorylation of downstream substrates of AKT was reduced in both sensitive and insensitive cell lines on treatment with GSK690693, suggesting that the cause of resistance was not related to the lack of AKT kinase inhibition. Consistent with the role of AKT in cell survival, GSK690693 also induced apoptosis in sensitive ALL cell lines. Overall, our data provides direct evidence for the role of AKT signaling in various hematological malignancies, especially ALL and some lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Iliopoulos, C. Polytarchou, M. Hatziapostolou, F. Kottakis, I. G. Maroulakou, K. Struhl, and P. N. Tsichlis MicroRNAs Differentially Regulated by Akt Isoforms Control EMT and Stem Cell Renewal in Cancer Cells Sci. Signal., October 13, 2009; 2(92): ra62 - ra62. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020