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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3666-3672. Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-02-0479. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0479v1 106/10/3666    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 Sconocchia, G. Articles by Barrett, A. J. Search for Related Content PubMed PubMed Citation Articles by Sconocchia, G. Articles by Barrett, A. J. Related Collections Neoplasia Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D–target-cell interactions Giuseppe Sconocchia, Michelle Lau, Maurizio Provenzano, Katayoun Rezvani, Wachanan Wongsena, Hiroshi Fujiwara, Nancy Hensel, Jos Melenhorst, Jonming Li, Soldano Ferrone, and A. John Barrett From the Stem Cell Allotransplantation Section, Hematology Branch, National Heart Lung and Blood Institute, and the Molecular Immunology Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD; and the Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY. To study natural killer (NK) cell–mediated antileukemic activity in chronic myelogenous leukemia (CML), we investigated the ability of HLA-matched and mismatched CD56+ cells to inhibit granulocyte macrophage–colony-forming unit (CFU-GM) formation by leukemic CD34+ cells. In 14 HLA-identical donor-recipient pairs, donor CD56+ cells inhibited CML CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% ± 9% vs 39.5% ± 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56+CD3- (natural killer [NK]) and CD56+CD3+(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34+ cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain–related gene A or gene B (MICA/B) on CML CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CML cells may avoid NK-cell–mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CML CD56+ cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] N. Dulphy, P. Haas, M. Busson, S. Belhadj, R. Peffault de Latour, M. Robin, M. Carmagnat, P. Loiseau, R. Tamouza, C. Scieux, et al. An Unusual CD56brightCD16low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation J. Immunol., August 1, 2008; 181(3): 2227 - 2237. [Abstract] [Full Text] [PDF] T. Zhang, A. Barber, and C. L. Sentman Chimeric NKG2D Modified T Cells Inhibit Systemic T-Cell Lymphoma Growth in a Manner Involving Multiple Cytokines and Cytotoxic Pathways Cancer Res., November 15, 2007; 67(22): 11029 - 11036. [Abstract] [Full Text] [PDF] M. Introna, G. Borleri, E. Conti, M. Franceschetti, A. M. Barbui, R. Broady, E. Dander, G. Gaipa, G. D'Amico, E. Biagi, et al. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study Haematologica, July 1, 2007; 92(7): 952 - 959. [Abstract] [Full Text] [PDF] N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al. BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia. J. Immunol., April 15, 2006; 176(8): 5108 - 5116. [Abstract] [Full Text] [PDF]

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