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Blood, 1 May 2007, Vol. 109, No. 9, pp. 4016-4019. Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-11-057521. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-057521v1 109/9/4016    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 Jørgensen, H. G. Articles by Holyoake, T. L. Search for Related Content PubMed PubMed Citation Articles by Jørgensen, H. G. Articles by Holyoake, T. L. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells Heather G. Jørgensen1, Elaine K. Allan1,2, Niove E. Jordanides1, Joanne C. Mountford1,2, and Tessa L. Holyoake1,2 1 Section of Experimental Haematology, Division of Cancer Sciences & Molecular Pathology, University of Glasgow, United Kingdom; 2 Academic Transfusion Medicine Unit, Scottish National Blood Transfusion Service, Glasgow, United Kingdom Chronic myeloid leukemia (CML) stem and progenitor cells overexpress BcrAbl and are insensitive to imatinib mesylate (IM). We therefore investigated whether these cells were efficiently targeted by nilotinib. In K562, the inhibitory concentration (IC50) of nilotinib was 30 nM versus 600 nM for IM, consistent with its reported 20-fold-higher potency. However, in primary CD34+ CML cells, nilotinib and IM were equipotent for inhibition of BcrAbl activity, producing equivalent but incomplete reduction in CrkL phosphorylation at 5 µM. CML CD34+ cells were still able to expand over 72 hours with 5 µM of either drug, although there was a concentration-dependent restriction of amplification. As for IM, the most primitive cells (CFSEmax) persisted and accumulated over 72 hours with nilotinib and remained caspase-3 negative. Furthermore, nilotinib with IM led to further accumulation of this population, suggesting at least additive antiproliferative effects. These results confirmed that, like IM, the predominant effect of nilotinib is antiproliferative rather than proapoptotic. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Pellicano, M. Copland, H. G. Jorgensen, J. Mountford, B. Leber, and T. L. Holyoake BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38- cells, through activation of protein kinase C{beta} Blood, November 5, 2009; 114(19): 4186 - 4196. [Abstract] [Full Text] [PDF] A. Quintas-Cardama and J. Cortes Molecular biology of bcr-abl1-positive chronic myeloid leukemia Blood, February 19, 2009; 113(8): 1619 - 1630. [Abstract] [Full Text] [PDF] A. S. M. Yong, K. Keyvanfar, N. Hensel, R. Eniafe, B. N. Savani, M. Berg, A. Lundqvist, S. Adams, E. M. Sloand, J. M. Goldman, et al. Primitive quiescent CD34+ cells in chronic myeloid leukemia are targeted by in vitro expanded natural killer cells, which are functionally enhanced by bortezomib Blood, January 22, 2009; 113(4): 875 - 882. [Abstract] [Full Text] [PDF] R. Zhao, G. A. Follows, P. A. Beer, L. M. Scott, B. J.P. Huntly, A. R. Green, and D. R. Alexander Inhibition of the Bcl-xL Deamidation Pathway in Myeloproliferative Disorders N. Engl. J. Med., December 25, 2008; 359(26): 2778 - 2789. [Abstract] [Full Text] [PDF] M. Copland, F. Pellicano, L. Richmond, E. K. Allan, A. Hamilton, F. Y. Lee, R. Weinmann, and T. L. Holyoake BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors Blood, March 1, 2008; 111(5): 2843 - 2853. [Abstract] [Full Text] [PDF] J. V. Melo and C. Chuah Novel Agents in CML Therapy: Tyrosine Kinase Inhibitors and Beyond Hematology, January 1, 2008; 2008(1): 427 - 435. [Abstract] [Full Text] [PDF] C. H. Jamieson Chronic Myeloid Leukemia Stem Cells Hematology, January 1, 2008; 2008(1): 436 - 442. [Abstract] [Full Text] [PDF] T. O'Hare, C. A. Eide, and M. W. N. Deininger Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia Blood, October 1, 2007; 110(7): 2242 - 2249. [Abstract] [Full Text] [PDF] H. Modi, T. McDonald, S. Chu, J.-K. Yee, S. J. Forman, and R. Bhatia Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells Blood, June 15, 2007; 109(12): 5411 - 5421. [Abstract] [Full Text] [PDF]

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