SEARCH:   Advanced

Blood, 15 December 2004, Vol. 104, No. 13, pp. 4219-4225. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-04-1433. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1433v1 104/13/4219    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 Yin, T. Articles by Chen, Z. Search for Related Content PubMed PubMed Citation Articles by Yin, T. Articles by Chen, Z. Related Collections Oncogenes and Tumor Suppressors Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Combined effects of As4S4 and imatinib on chronic myeloid leukemia cells and BCR-ABL oncoprotein Tong Yin, Ying-Li Wu, Hui-Ping Sun, Guan-Lin Sun, Yan-Zhi Du, Kan-Kan Wang, Ji Zhang, Guo-Qiang Chen, Sai-Juan Chen, and Zhu Chen From the State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, and the Department of Hematology, Ruijin Hospital, Shanghai Second Medical University (SSMU); the Department of Medical Laboratory Science, Ruijin Medical College of SSMU; the Department of Pathophysiology, SSMU; and the Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, and SSMU, Shanghai, China. Imatinib (STI571, Gleevec) is a tailored drug for chronic myelogenous leukemia (CML), whereas arsenic compounds were used as ancient remedies for CML with certain efficacy. The aim of this study was to investigate the potential benefit of combination therapy with imatinib and arsenic sulfide (As4S4). Analysis of cell proliferation and clonogenic ability showed that As4S4 and imatinib exerted synergistic effects on both K562 cells and fresh CML cells. The effective concentrations on fresh CML cells were pharmacokinetically available in vivo but had much less inhibitory effect on CD34+ cells from the nonleukemic donors. Examination of cell cycles showed that As4S4 induced G2/M arrest whereas imatinib induced G1 arrest. Using a number of parameters such as morphology, annexin V/propidium iodide (PI), mitochondrial transmembrane potential, caspase-3 activity, and Fas/Fas-L, the synergistic effects were revealed on induction of cell apoptosis, largely through the mitochondrial pathway. The 2 drugs also exhibited a synergistic effect in targeting BCR-ABL protein. While As4S4 triggered its degradation and imatinib inhibited its tyrosine kinase activity, combined use of the 2 led to lower protein/enzymatic activity levels of BCR-ABL. Our in vitro data thus strongly suggest a potential clinical application of imatinib and As4S4 combination on CML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Du, K. Wang, H. Fang, J. Li, D. Xiao, P. Zheng, Y. Chen, H. Fan, X. Pan, C. Zhao, et al. Coordination of intrinsic, extrinsic, and endoplasmic reticulum-mediated apoptosis by imatinib mesylate combined with arsenic trioxide in chronic myeloid leukemia Blood, February 15, 2006; 107(4): 1582 - 1590. [Abstract] [Full Text] [PDF] T. O'Hare, D. K. Walters, E. P. Stoffregen, D. W. Sherbenou, M. C. Heinrich, M. W.N. Deininger, and B. J. Druker Combined Abl Inhibitor Therapy for Minimizing Drug Resistance in Chronic Myeloid Leukemia: Src/Abl Inhibitors Are Compatible with Imatinib Clin. Cancer Res., October 1, 2005; 11(19): 6987 - 6993. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020