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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3615-3622. Prepublished online as a Blood First Edition Paper on January 18, 2005; DOI 10.1182/blood-2004-07-2585. This Article Full Text (PDF) Supplemental Data All Versions of this Article: 2004-07-2585v1 105/9/3615    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nowbakht, P. Articles by Wodnar-Filipowicz, A. Search for Related Content PubMed PubMed Citation Articles by Nowbakht, P. Articles by Wodnar-Filipowicz, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2004 Accepted December 22, 2004 Ligands for natural killer cell activating receptors are expressed upon maturation of normal myelomonocytic cells but are low in acute myeloid leukemias Pegah Nowbakht, Mihai-Constantin S Ionescu, Andreas Rohner, Christian P Kalberer, Emmanuel Rossy, Lucia Mori, David Cosman, Gennaro De Libero, and Aleksandra Wodnar-Filipowicz* Experimental Hematology and Experimental Immunology, Department of Research, University Hospital Basel, Basel, Switzerland Amgen Washington Inc., Seattle, WA, USA * Corresponding author; email: Aleksandra.Wodnar-Filipowicz{at}unibas.ch. Natural killer (NK) cell-mediated cytolytic activity against tumors requires the engagement of activating NK receptors by the tumor-associated ligands. Here, we studied the role of NKG2D and natural cytotoxicity receptors (NCRs) in the recognition of human leukemia. To detect as yet unknown cell surface molecules recognized by NCRs, we developed soluble forms of NKp30, NKp44 and NKp46 as staining reagents binding the putative cognate ligands. Analysis of ULBP1, ULBP2 and ULBP3 ligands for NKG2D and of potential ligands for NKp30, NKp44 and NKp46 in healthy hematopoietic cells demonstrated the ligand-negative phenotype of bone marrow-derived CD34+ progenitor cells and the acquisition of cell surface ligands during the course of myeloid differentiation. In acute myeloid leukemia (AML), leukemic blasts from about 80% of patients expressed very low levels of ULBPs and NCR-specific ligands. Treatment with differentiation-promoting myeloid growth factors together with interferon-gamma upregulated cell surface levels of ULBP1 and putative NCR ligands on AML blasts, conferring an increased sensitivity to NK cell-mediated lysis. We conclude that the ligand-negative/low phenotype in AML is a consequence of cell maturation arrest upon malignant transformation and that defective expression of ligands for the activating NKG2D and NCR receptors may compromise leukemia recognition by NK cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Langenkamp, U. Siegler, S. Jorger, S. Diermayr, A. Gratwohl, C. P. Kalberer, and A. Wodnar-Filipowicz Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells Haematologica, November 1, 2009; 94(11): 1590 - 1594. [Abstract] [Full Text] [PDF] X. Xu, K. Tsumagari, J. Sowden, R. Tawil, A. P. Boyle, L. Song, T. S. Furey, G. E. Crawford, and M. Ehrlich DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2 Nucleic Acids Res., October 9, 2009; (2009) gkp833v1. [Abstract] [Full Text] [PDF] C. S. Brandt, M. 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NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities Blood, February 1, 2008; 111(3): 1428 - 1436. [Abstract] [Full Text] [PDF] C. Cerboni, A. Zingoni, M. Cippitelli, M. Piccoli, L. Frati, and A. Santoni Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis Blood, July 15, 2007; 110(2): 606 - 615. [Abstract] [Full Text] [PDF] P. Saikali, J. P. Antel, J. Newcombe, Z. Chen, M. Freedman, M. Blain, R. Cayrol, A. Prat, J. A. Hall, and N. Arbour NKG2D-Mediated Cytotoxicity toward Oligodendrocytes Suggests a Mechanism for Tissue Injury in Multiple Sclerosis J. Neurosci., January 31, 2007; 27(5): 1220 - 1228. [Abstract] [Full Text] [PDF] J. North, I. Bakhsh, C. Marden, H. Pittman, E. Addison, C. Navarrete, R. Anderson, and M. W. 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