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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3746-3753. Prepublished online as a Blood First Edition Paper on August 10, 2004; DOI 10.1182/blood-2004-05-1941. This Article Full Text (PDF) All Versions of this Article: 2004-05-1941v1 104/12/3746    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nowicki, M. O Articles by Skorski, T. Search for Related Content PubMed PubMed Citation Articles by Nowicki, M. O Articles by Skorski, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 25, 2004 Accepted July 27, 2004 BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species - dependent DNA double-strand breaks Michal O Nowicki, Rafal Falinski, Mateusz Koptyra, Artur Slupianek, Tomasz Stoklosa, Ewa Gloc, Margaret Nieborowska-Skorska, Janusz Blasiak, and Tomasz Skorski* Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA; Department of Immunology, Medical University of Warsaw, Warsaw, Poland Department of Molecular Genetics, University of Lodz, Lodz, Poland * Corresponding author; email: tskorski{at}temple.edu. The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph1)-positive leukemia cells. We find that BCR/ABL-induced reactive oxygen species (ROS) cause chronic oxidative DNA damage resulting in replication fork-dependent double-strand breaks (DSBs). These lesions are repaired by BCR/ABL-stimulated homologous recombination repair (HRR) and non-homologous end-joining (NHEJ) mechanisms. A high mutation rate is detected in HRR products in BCR/ABL-positive cells, but not in the normal counterparts. In addition, large deletions are found in NHEJ products exclusively in BCR/ABL cells. We propose that the following series of events may contribute to genomic instability of Ph1-positive leukemias: BCR/ABL ROS oxidative DNA damage DSBs in proliferating cells unfaithful HRR and NHEJ repair. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Genetic rearrangements beget genomic instability Feyruz V. Rassool Blood 2004 104: 3424-3425. [Full Text] [PDF]

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