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Blood, 15 July 2004, Vol. 104, No. 2, pp. 356-363. Prepublished online as a Blood First Edition Paper on March 23, 2004; DOI 10.1182/blood-2003-06-1948. This Article Full Text (PDF) All Versions of this Article: 2003-06-1948v1 104/2/356    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 Soda, Y. Articles by Asano, S. Search for Related Content PubMed PubMed Citation Articles by Soda, Y. Articles by Asano, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 20, 2003 Accepted February 1, 2004 A novel Maxizyme vector targeting a bcr-abl fusion gene induced specific cell death in Philadelphia chromosome-positive acute lymphoblastic leukemia Yasushi Soda, Kenzaburo Tani*, Yuansong Bai, Minoru Saiki, Minghan Chen, Kiyoko Izawa, Seiichiro Kobayashi, Satoshi Takahashi, Kaoru Uchimaru, Tomoko Kuwabara, Masaaki Warashina, Tsuyoshi Tanabe, Hiroyuki Miyoshi, Kanji Sugita, Shinpei Nakazawa, Arinobu Tojo, Kazunari Taira, and Shigetaka Asano Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Department of Advanced Molecular and Cell Therapy,Department of Molecular Genetics, Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Department of Internal Medicine Division 1, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan Subteam for Manipulation of Cell Fate, BioResource Center, Tsukuba institute, The Institute of Physical and Chemical Research(RIKEN), Tsukuba, Ibaraki, Japan Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Tamao, Yamanashi/Nakakoma-gun, Japan Department of Internal Medicine Division 1, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan; Department of Chemistry and Biotechnology, Graduate School of Engineering, Bunkyo-ku, Tokyo, Japan * Corresponding author; email: taniken{at}bioreg.kyushu-u.ac.jp. Patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) generally have a poor prognosis and would benefit from the development of new therapeutic approaches. We previously demonstrated that an allosterically controllable ribozyme, Maxizyme (Mz), can induce apoptosis in chronic myelogenous leukemia (CML) cells. Ph+ ALL cells harbor a bcr-abl fusion gene (e1a2) encoding a 190-kD fusion protein (p190) involved disease pathogenesis. In this study, we have designed a Mz that specifically cleaves e1a2 mRNA and transduced this e1a2Mz into Ph+ ALL cells using a third-generation lentiviral vector system. In three of five Ph+ ALL cell lines, e1a2Mz transduction resulted in a significant decrease in viability and increased cell apoptosis. We observed a decrease in e1a2 mRNA in all Ph+ ALL cells transduced with e1a2Mz, and the e1a2 mRNA level was higher in e1a2Mz-resistant cells than in e1a2Mz-sensitive cells. All samples of primary Ph+ ALL cells tested showed e1a2Mz-induced growth inhibition and apoptosis. Importantly, e1a2Mz did not influence the colony formation of normal CD34+ cord blood cells. These results indicate that e1a2Mz kills Ph+ ALL cells specifically, suggesting that it may be used as a novel gene therapy strategy for Ph+ ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Harata, Y. Soda, K. Tani, J. Ooi, T. Takizawa, M. Chen, Y. Bai, K. Izawa, S. Kobayashi, A. Tomonari, et al. CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells Blood, September 1, 2004; 104(5): 1442 - 1449. [Abstract] [Full Text] [PDF]

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