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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3963-3971. Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-09-045583. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-09-045583v1 109/9/3963    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 Boyapati, A. Articles by Zhang, D.-E. Search for Related Content PubMed PubMed Citation Articles by Boyapati, A. Articles by Zhang, D.-E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 5, 2006 Accepted December 16, 2006 A leukemia fusion protein attenuates the spindle checkpoint and promotes aneuploidy Anita Boyapati, Ming Yan, Luke F. Peterson, Joseph R. Biggs, Michelle M. Le Beau, and Dong-Er Zhang* Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA Section of Hematology/Oncology & the Cancer Research Center, University of Chicago, Chicago, IL * Corresponding author; email: dzhang{at}scripps.edu. The 8;21 chromosomal translocation occurs in 15-40% of patients with the FAB M2 subtype of acute myeloid leukemia. This chromosomal abnormality fuses part of the AML1/RUNX1 gene to the ETO/MTG8 gene and generates the AML1-ETO protein. We previously identified a C-terminal truncated AML1-ETO protein (AEtr) in a mouse leukemia model. AEtr is almost identical to the AML1-ETO exon 9a isoform expressed in leukemia patients. Here, we describe a novel function of AEtr in the development of aneuploidy through spindle checkpoint attenuation. AEtr cells had a reduced mitotic index following nocodazole treatment, suggesting a failure in a subset of cells to arrest in mitosis with a functional spindle checkpoint. Additionally, primary leukemia cells and cell lines expressing AEtr were aneuploid. Moreover, AEtr cells had reduced levels of several spindle checkpoint proteins including BubR1 and securin following treatment with the spindle poison nocodazole. These results suggest that inactivation of the spindle checkpoint may contribute to the development of aneuploidy described in t(8;21) leukemia patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E.-Y. Ahn, M. Yan, O. A. Malakhova, M.-C. Lo, A. Boyapati, H. B. Ommen, R. Hines, P. Hokland, and D.-E. Zhang Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis PNAS, November 4, 2008; 105(44): 17103 - 17108. [Abstract] [Full Text] [PDF] A. J. Okumura, L. F. Peterson, F. Okumura, A. Boyapati, and D.-E. Zhang t(8;21)(q22;q22) fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression Blood, August 15, 2008; 112(4): 1392 - 1401. [Abstract] [Full Text] [PDF] O. Krejci, M. Wunderlich, H. Geiger, F.-S. Chou, D. Schleimer, M. Jansen, P. R. Andreassen, and J. C. Mulloy p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death Blood, February 15, 2008; 111(4): 2190 - 2199. [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]

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