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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3441-3450. Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-06-032250. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-06-032250v1 109/8/3441    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 Zhou, G.-B. Articles by Chen, Z. Search for Related Content PubMed PubMed Citation Articles by Zhou, G.-B. Articles by Chen, Z. Related Collections Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo Guang-Biao Zhou1,2, Hui Kang1, Lan Wang1,3, Li Gao1, Ping Liu1, Jun Xie2, Feng-Xiang Zhang2, Xiang-Qin Weng1, Zhi-Xiang Shen1, Jue Chen1, Long-Jun Gu4, Ming Yan5, Dong-Er Zhang5, Sai-Juan Chen1,3, Zhen-Yi Wang1, and Zhu Chen1,3 1 State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China; 2 Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; 3 Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; 4 Children's Medical Center, SJTUSM, Shanghai, China; 5 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA Studies have documented the potential antitumor activities of oridonin, a compound extracted from medicinal herbs. However, whether oridonin can be used in the selected setting of hematology/oncology remains obscure. Here, we reported that oridonin induced apoptosis of t(8;21) acute myeloid leukemic (AML) cells. Intriguingly, the t(8;21) product AML1-ETO (AE) fusion protein, which plays a critical role in leukemogenesis, was degraded with generation of a catabolic fragment, while the expression pattern of AE target genes investigated could be reprogrammed. The ectopic expression of AE enhanced the apoptotic effect of oridonin in U937 cells. Preincubation with caspase inhibitors blocked oridonin-triggered cleavage of AE, while substitution of Ala for Asp at residues 188 in ETO moiety of the fusion abrogated AE degradation. Furthermore, oridonin prolonged lifespan of C57 mice bearing truncated AE-expressing leukemic cells without suppression of bone marrow or reduction of body weight of animals, and exerted synergic effects while combined with cytosine arabinoside. Oridonin also inhibited tumor growth in nude mice inoculated with t(8;21)-harboring Kasumi-1 cells. These results suggest that oridonin may be a potential antileukemia agent that targets AE oncoprotein at residue D188 with low adverse effect, and may be helpful for the treatment of patients with t(8;21) AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, G.-B. Zhou, P. Liu, J.-H. Song, Y. Liang, X.-J. Yan, F. Xu, B.-S. Wang, J.-H. Mao, Z.-X. Shen, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia PNAS, March 25, 2008; 105(12): 4826 - 4831. [Abstract] [Full Text] [PDF] L. F. Peterson, A. Boyapati, E.-Y. Ahn, J. R. Biggs, A. J. Okumura, M.-C. Lo, M. Yan, and D.-E. Zhang Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts Blood, August 1, 2007; 110(3): 799 - 805. [Abstract] [Full Text] [PDF] K. Petrie and A. Zelent AML1/ETO, a promiscuous fusion oncoprotein Blood, May 15, 2007; 109(10): 4109 - 4110. [Full Text] [PDF]

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