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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-10-3011. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3011v1 101/11/4583    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 Deutsch, E. Articles by Bourhis, J. Search for Related Content PubMed PubMed Citation Articles by Deutsch, E. Articles by Bourhis, J. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4583-4588 NEOPLASIA Down-regulation of BRCA1 in BCR-ABL–expressing hematopoietic cells Eric Deutsch, Sylvie Jarrousse, Dorothée Buet, Aymeric Dugray, Marie-Laure Bonnet, Marie-Catherine Vozenin-Brotons, François Guilhot, Ali G. Turhan, Jean Feunteun, and Jean Bourhis From the Unité propre de la recherche et de l'enseignement supérieur (UPRES) EA 27-10 Radiosensibilité des tumeurs et des tissus sains, Unité mixte de Recherche (UMR) 8125 Génétique Oncologique, Institut National de la Santé et de la recherche médicale (INSERM) U362, Translational Research-Cell Therapy Laboratory, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France; and Departement d'Oncology-Hematologie and Cell Therapy, Poitiers, France. BCR-ABL fusion oncogene is the molecular hallmark of chronic myelogenous leukemia (CML), a condition characterized by a progression from a chronic to acute phase leukemia because of secondary genetic events, the nature of which remains largely unknown. Here, we report that the expression of the p210 BCR-ABL fusion protein leads to a down-regulation of BRCA1 protein, a gene product involved in the maintenance of genome integrity. BRCA1 protein is nearly undetectable in leukemia cells from patients with CML, both during the chronic phase and in blast crisis. Similarly, stable transfection-enforced expression of p210 protein in established hematopoietic cell lines leads to severe BRCA1 depletion. The lack of significant change in BRCA1 mRNA level in cells expressing p210 supports the hypothesis that the regulation of BRCA1 protein level occurs after transcription. It is abolished on exposure of the cells to STI571 and by mutation in the adenosine triphosphate (ATP) pocket of p210 and thus seems to require the tyrosine kinase activity of BCR-ABL. Cell lines expressing high levels of BCR-ABL display an increased rate of sister chromatid exchange and chromosome aberrations after ionizing radiation. These findings reveal a novel link between the oncoprotein BCR-ABL and the tumor-suppressor protein BRCA1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-J. Zhang, L.-Y. Ma, Q.-H. Huang, G. Li, B.-W. Gu, X.-D. Gao, J.-Y. Shi, Y.-Y. Wang, L. Gao, X. Cai, et al. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia PNAS, February 12, 2008; 105(6): 2076 - 2081. [Abstract] [Full Text] [PDF] F. Huguet, N. Giocanti, C. Hennequin, M. Croisy, E. Touboul, and V. Favaudon Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells Mol. Cancer Ther., February 1, 2008; 7(2): 398 - 406. [Abstract] [Full Text] [PDF] H.-J. Chung, H.-S. Chi, Y.-U. Cho, C.-J. Park, E. J. Seo, K.-H. Kim, and J.-H. Lee Promyelocytic Blast Crisis of Chronic Myeloid Leukemia during Imatinib Treatment Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 283 - 286. [Abstract] [Full Text] [PDF] P. J. LeRoy, J. J. Hunter, K. M. Hoar, K. E. Burke, V. Shinde, J. Ruan, D. Bowman, K. Galvin, and J. A. Ecsedy Localization of Human TACC3 to Mitotic Spindles Is Mediated by Phosphorylation on Ser558 by Aurora A: A Novel Pharmacodynamic Method for Measuring Aurora A Activity Cancer Res., June 1, 2007; 67(11): 5362 - 5370. [Abstract] [Full Text] [PDF] R. L. Ilaria Jr. Pathobiology of Lymphoid and Myeloid Blast Crisis and Management Issues Hematology, January 1, 2005; 2005(1): 188 - 194. [Abstract] [Full Text] [PDF] M. O. Nowicki, R. Falinski, M. Koptyra, A. Slupianek, T. Stoklosa, E. Gloc, M. Nieborowska-Skorska, J. Blasiak, and T. Skorski BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks Blood, December 1, 2004; 104(12): 3746 - 3753. [Abstract] [Full Text] [PDF] B. Calabretta and D. Perrotti The biology of CML blast crisis Blood, June 1, 2004; 103(11): 4010 - 4022. [Abstract] [Full Text] [PDF]

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