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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2002-12-3656. This Article Full Text (PDF) All Versions of this Article: 2002-12-3656v1 102/9/3317    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 Kamio, T. Articles by Ito, E. Search for Related Content PubMed PubMed Citation Articles by Kamio, T. Articles by Ito, E. Social Bookmarking                   What's this? Submitted January 6, 2003 Accepted May 10, 2003 The B cell-specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs Takuya Kamio, Tsutomu Toki, Rika Kanezaki, Shinya Sasaki, Satoru Tandai, Kiminori Terui, Dai Ikebe, Kazuhiko Igarashi, and Etsuro Ito* Pediatrics, Hirosaki University, Hirosaki, Japan Biochemistry, Hiroshima University, Hiroshima, Japan * Corresponding author; email: eturou{at}cc.hirosaki-u.ac.jp. The transcription factor Bach2, a member of the CNC family of proteins, binds to the Maf Recognition Element (MARE) by forming homodimers or dimerizing with small Maf transcription factors. Bach2-expressing cells show reduced proliferation and undergo spontaneous cell death. The inhibition of BCR/ABL tyrosine kinase activity by STI571 in chronic myeloid leukemia (CML) cell lines and CD34+ cells from CML patients in lymphoid crisis results in induction of BACH2 expression. We show here that BACH2 modifies the in vitro cytotoxicity of anticancer drugs. The cytotoxic effects of commonly used anticancer agents were studied by overexpression of BACH2 in RAJI lymphoid cells, a cell line that does not express endogenous BACH2. Cell growth inhibition was determined by MTT assay. Clones overexpressing BACH2 were more sensitive to etoposide, doxorubicin, and cytarabine than control RAJI cells, whereas there were no significant differences in the sensitivity of either cells to methotrexate or vincristine. Interestingly, we found that the former drugs were oxidative stressors that induced the nuclear accumulation of BACH2. In contrast, methotrexate or vincristine did not induce production of intracellular reactive oxygen species (ROS) and nuclear accumulation of BACH2. These results, coupled with our previous data showing that BACH2 promotes oxidative stress-induced cell death, suggest that combination chemotherapy involving STI571 and anticancer drugs that produce ROS may be of benefit in the treatment of Ph1-positive leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Garcia-Manero, H. Yang, C. Bueso-Ramos, A. Ferrajoli, J. Cortes, W. G. Wierda, S. Faderl, C. Koller, G. Morris, G. Rosner, et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Blood, February 1, 2008; 111(3): 1060 - 1066. [Abstract] [Full Text] [PDF] K. Igarashi, K. Ochiai, and A. Muto Architecture and Dynamics of the Transcription Factor Network that Regulates B-to-Plasma Cell Differentiation J. Biochem., June 1, 2007; 141(6): 783 - 789. [Abstract] [Full Text] [PDF] H. 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