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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-08-2675. This Article Full Text (PDF) All Versions of this Article: 2002-08-2675v1 101/8/3236    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 Nimmanapalli, R. Articles by Bhalla, K. Search for Related Content PubMed PubMed Citation Articles by Nimmanapalli, R. Articles by Bhalla, K. Social Bookmarking                   What's this? Submitted September 6, 2002 Accepted November 14, 2002 Co-treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances Gleevec-induced apoptosis of Bcr-Abl positive human acute leukemia cells Ramadevi Nimmanapalli, Lianne Fuino, Corinne Stobaugh, Victoria M Richon, and Kapil Bhalla* Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA Aton Pharma, Inc., Tarrytown, NY, USA * Corresponding author; email: bhallakn{at}moffitt.usf.edu. Here we demonstrate that treatment with SAHA (Suberoylanilide hydroxamic acid), a known inhibitor of histone deacetylases (HDACs), alone induced p21 and/or p27 expressions, but decreased the mRNA and protein levels of Bcr-Abl, which was associated with apoptosis of Bcr-Abl expressing K562 and LAMA-84 cells. Co-treatment with SAHA and Gleevec caused more downregulation of the levels and auto-tyrosine phosphorylation of Bcr-Abl and apoptosis of these cell-types, as compared to treatment with either agent alone (p<0.05). This was also associated with a greater decline in the levels of phospho-AKT and Bcl-xL. Significantly, treatment with SAHA also downregulated Bcr-Abl levels and induced apoptosis of CD34+ leukemia blast progenitor cells derived from patients who had developed progressive blast crisis (BC) of CML while receiving therapy with Gleevec. Taken together, these findings indicate that co-treatment with SAHA enhances the cytotoxic effects of Gleevec and may have activity against Gleevec-refractory CML-BC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. W. Schaefer, A. Loaiza-Bonilla, M. Juckett, J. F. DiPersio, V. Roy, J. Slack, W. Wu, K. Laumann, I. Espinoza-Delgado, S. D. Gore, et al. 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Oncol., May 20, 2007; 25(15): 1955 - 1956. [Full Text] [PDF] P. Munster, D. Marchion, E. Bicaku, M. Schmitt, J. H. Lee, R. DeConti, G. Simon, M. Fishman, S. Minton, C. Garrett, et al. Phase I Trial of Histone Deacetylase Inhibition by Valproic Acid Followed by the Topoisomerase II Inhibitor Epirubicin in Advanced Solid Tumors: A Clinical and Translational Study J. Clin. Oncol., May 20, 2007; 25(15): 1979 - 1985. [Abstract] [Full Text] [PDF] L. M. Greene, L. Kelly, V. Onnis, G. Campiani, M. Lawler, D. C. Williams, and D. M. Zisterer STI-571 (Imatinib Mesylate) Enhances the Apoptotic Efficacy of Pyrrolo-1,5-Benzoxazepine-6, a Novel Microtubule-Targeting Agent, in Both STI-571-Sensitive and -Resistant Bcr-Abl-Positive Human Chronic Myeloid Leukemia Cells J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 288 - 297. [Abstract] [Full Text] [PDF] I. Gojo, A. Jiemjit, J. B. Trepel, A. Sparreboom, W. D. Figg, S. Rollins, M. L. Tidwell, J. Greer, E. J. Chung, M.-J. Lee, et al. 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Pharmacol., October 1, 2005; 68(4): 917 - 932. [Abstract] [Full Text] [PDF] J. Cortes and H. Kantarjian New Targeted Approaches in Chronic Myeloid Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6316 - 6324. [Abstract] [Full Text] [PDF] K. N. Bhalla Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies J. Clin. Oncol., June 10, 2005; 23(17): 3971 - 3993. [Abstract] [Full Text] [PDF] T. Maeda, F. Yagasaki, M. Ishikawa, N. Takahashi, and M. Bessho Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML Blood, March 1, 2005; 105(5): 2115 - 2123. [Abstract] [Full Text] [PDF] A. Moldenhauer, R. C. Frank, J. Pinilla-Ibarz, G. Holland, P. Boccuni, D. A. Scheinberg, A. Salama, K. Seeger, M. A. S. Moore, and S. D. Nimer Histone deacetylase inhibition improves dendritic cell differentiation of leukemic blasts with AML1-containing fusion proteins J. Leukoc. Biol., September 1, 2004; 76(3): 623 - 633. 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Gasparetto, M. Glozak, J. Tao, L. Moscinski, C. Smith, J. Wu, R. Jove, et al. Histone Deacetylase Inhibitor LAQ824 Both Lowers Expression and Promotes Proteasomal Degradation of Bcr-Abl and Induces Apoptosis of Imatinib Mesylate-sensitive or -refractory Chronic Myelogenous Leukemia-Blast Crisis Cells Cancer Res., August 15, 2003; 63(16): 5126 - 5135. [Abstract] [Full Text] [PDF]

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