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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2985-2993. Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-03-0811. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0811v1 102/8/2985    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 Beissert, T. Articles by Ruthardt, M. Search for Related Content PubMed PubMed Citation Articles by Beissert, T. Articles by Ruthardt, M. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Targeting of the N-terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR-ABL and increases sensitivity to STI571 Tim Beissert, Elena Puccetti, Andrea Bianchini, Saskia Güller, Simone Boehrer, Dieter Hoelzer, Oliver Gerhard Ottmann, Clara Nervi, and Martin Ruthardt From the Med. Klinik III/Abtl. Hämatologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany; Dipartimento di Istologia ed Embriologia Medica, Università "La Sapienza," Rome, Italy; and the Institute of Cell Biology and Tissue Engineering, San Raffaele Bio-medical Science Park of Rome, Rome, Italy. Translocations involving the abl locus on chromosome 9 fuses the tyrosine kinase c-ABL to proteins harboring oligomerization interfaces such as BCR or TEL, enabling these ABL-fusion proteins (X-ABL) to transform cells and to induce leukemia. The ABL kinase activity is blocked by the ABL kinase inhibitor STI571 which abrogates transformation by X-ABL. To investigate the role of oligomerization for the transformation potential of X-ABL and for the sensitivity to STI571, we constructed ABL chimeras with oligomerization interfaces of proteins involved in leukemia-associated translocations such as BCR, TEL, PML, and PLZF. We assessed the capacity of these chimeras to form high molecular weight (HMW) complexes as compared with p185(BCR-ABL). There was a direct relationship between the size of HMW complexes formed by these chimeras and their capacity to induce factor independence in Ba/F3 cells, whereas there was an inverse relationship between the size of the HMW complexes and the sensitivity to STI571. The targeting of the oligomerization interface of p185(BCR-ABL) by a peptide representing the coiled coil region of BCR reduced its potential to transform fibroblasts and increased sensitivity to STI571. Our results indicate that targeting of the oligomerization interfaces of the X-ABL enhances the effects of STI571 in the treatment of leukemia caused by X-ABL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Wichmann, L. Chen, M. Heinrich, D. Baus, E. Pfitzner, M. Zornig, O. G. Ottmann, and M. Grez Targeting the Oligomerization Domain of ETO Interferes with RUNX1/ETO Oncogenic Activity in t(8;21)-Positive Leukemic Cells Cancer Res., March 1, 2007; 67(5): 2280 - 2289. [Abstract] [Full Text] [PDF] E. Puccetti, X. Zheng, D. Brambilla, A. Seshire, T. Beissert, S. Boehrer, H. Nurnberger, D. Hoelzer, O. G. Ottmann, C. Nervi, et al. The Integrity of the Charged Pocket in the BTB/POZ Domain Is Essential for the Phenotype Induced by the Leukemia-Associated t(11;17) Fusion Protein PLZF/RAR{alpha} Cancer Res., July 15, 2005; 65(14): 6080 - 6088. [Abstract] [Full Text] [PDF] C. E. Tognon, C. D. Mackereth, A. M. Somasiri, L. P. McIntosh, and P. H. B. Sorensen Mutations in the SAM Domain of the ETV6-NTRK3 Chimeric Tyrosine Kinase Block Polymerization and Transformation Activity Mol. Cell. Biol., June 1, 2004; 24(11): 4636 - 4650. [Abstract] [Full Text] [PDF]

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