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Blood, 15 January 2005, Vol. 105, No. 2, pp. 827-829. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-06-2125. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2125v1 105/2/827    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 Rassidakis, G. Z. Articles by Amin, H. M. Search for Related Content PubMed PubMed Citation Articles by Rassidakis, G. Z. Articles by Amin, H. M. Related Collections Neoplasia Cell Cycle Oncogenes and Tumor Suppressors Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma George Z. Rassidakis, Marianna Feretzaki, Coralyn Atwell, Ioannis Grammatikakis, Quan Lin, Raymond Lai, Francois-Xavier Claret, L. Jeffrey Medeiros, and Hesham M. Amin From the Departments of Hematopathology and Molecular Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX; and Department of Laboratory Medicine and Pathology, University of Alberta and Cross Cancer Institute Edmonton, Alberta, Canada. Anaplastic large cell lymphoma (ALCL) is a highly proliferative neoplasm that frequently carries the t(2;5)(p23;q35) and aberrantly expresses nucleophosmin–anaplastic lymphoma kinase (NPM-ALK). Previously, NPM-ALK had been shown to activate the phosphatidylinositol 3 kinase (PI3K)/Akt pathway. As the cyclin-dependent kinase (CDK) inhibitor p27Kip1 (p27) is usually not expressed in ALCL, we hypothesized that activated Akt (pAkt) phosphorylates p27 resulting in increased p27 proteolysis and cell cycle progression. Here we demonstrate that inhibition of pAkt activity in ALCL decreases p27 phosphorylation and degradation, resulting in increased p27 levels and cell cycle arrest. Using immunohistochemistry, pAkt was detected in 24 (57%) of 42 ALCL tumors, including 8 (44%) of 18 ALK-positive tumors and 16 (67%) of 24 ALK-negative tumors, and was inversely correlated with p27 levels. The mean percentage of p27-positive tumor cells was 5% in the pAkt-positive group compared with 26% in the pAkt-negative group (P = .0076). These findings implicate that Akt activation promotes cell cycle progression through inactivation of p27 in ALCL. 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