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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4003-4010. Prepublished online as a Blood First Edition Paper on February 9, 2006; DOI 10.1182/blood-2005-04-1523. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-04-1523v1 107/10/4003    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 Piwocka, K. Articles by McKenna, S. L. Search for Related Content PubMed PubMed Citation Articles by Piwocka, K. Articles by McKenna, S. L. Related Collections Immunobiology Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Bcr-Abl reduces endoplasmic reticulum releasable calcium levels by a Bcl-2–independent mechanism and inhibits calcium-dependent apoptotic signaling Katarzyna Piwocka, Susanne Vejda, Thomas G. Cotter, Gerald C. O'Sullivan, and Sharon L. McKenna From the Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland; and Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College Cork, Cork, Ireland, and the Necki Institute of Experimental Biology, Warsaw, Poland. The Bcr-Abl oncoprotein plays a major role in the development and progression of chronic myeloid leukemia (CML). Several studies have suggested that the expression levels of Bcr-Abl are elevated at disease progression to blast crisis and that this plays a significant role in the achievement of drug resistance. We have established cell lines expressing low and high levels of Bcr-Abl to study the molecular mechanisms involved in disease progression and drug resistance. It is now known that the endoplasmic reticulum (ER) can play a major role in the regulation of apoptosis. We therefore investigated whether Bcr-Abl expression modulates ER homeostasis and interferes with ER-mediated apoptotic pathways to promote survival. Bcr-Abl–expressing cells exhibit a decreased amount of free releasable calcium in the ER as well as a weaker capacitative calcium entry response, relative to parental cells. This effect is independent of Bcl-2, which is a known modulator of ER calcium homeostasis. The reduction in ER releasable calcium results in inhibition of the ER/mitochondria-coupling process and mitochondrial calcium uptake. This study demonstrates a novel downstream consequence of Bcr-Abl signaling. The ability to negate calcium-dependent apoptotic signaling is likely to be a major prosurvival mechanism in Bcr-Abl–expressing cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. S. Han, K. W. Chung, H. G. Cheon, S. D. Rhee, C.-H. Yoon, M.-K. Lee, K.-W. Kim, and M.-S. Lee Imatinib Mesylate Reduces Endoplasmic Reticulum Stress and Induces Remission of Diabetes in db/db Mice Diabetes, February 1, 2009; 58(2): 329 - 336. [Abstract] [Full Text] [PDF]

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