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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1428-1436. Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-07-101311. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-07-101311v1 111/3/1428    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 Diermayr, S. Articles by Wodnar-Filipowicz, A. Search for Related Content PubMed PubMed Citation Articles by Diermayr, S. Articles by Wodnar-Filipowicz, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 16, 2007 Accepted November 3, 2007 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 Stefan Diermayr, Heike Himmelreich, Bojana Durovic, Arina Mathys-Schneeberger, Uwe Siegler, Ulrich Langenkamp, Jan Hofsteenge, Alois Gratwohl, Andre Tichelli, Monika Paluszewska, Wieslaw Wiktor-Jedrzejczak, Christian P Kalberer, and Aleksandra Wodnar-Filipowicz* Department of Research, University Hospital Basel, Basel, Switzerland Stem Cell Transplant Team, University Hospital Basel, Basel, Switzerland Growth Control, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland Department of Hematology and Oncology, Medical University of Warsaw, Warsaw, Poland * Corresponding author; email: aleksandra.wodnar-filipowicz{at}unibas.ch. This study exploited alloreactivity of natural killer (NK) cells for augmenting the recognition of human acute myeloid leukemia (AML). To circumvent the inhibitory effect of killer immunoglobulin receptor (KIR) signaling, we generated NK cell lines with single KIR specificities for the major HLA-class I allotypes. We demonstrated efficient cytolysis of KIR-HLA-class I-mismatched primary AML blasts even at low effector to target ratios. To define the impact of tumor-associated activating NKG2D-ligands (NKG2D-L), 66 AML patients at diagnosis were analysed. NKG2D-L were selectively expressed on monoblastic cells in AML M4 and M5, whereas absent or weakly expressed on myeloblastic cells in all AML subtypes. Paucicity of cell surface NKG2D-L was not due to shedding since levels of soluble ULBP1, the prominent NKGD-L family member, measured in AML plasma were in normal range. Notably, purified NKG2D-L+ monoblastic cells were more susceptible to NK-mediated killing than NKG2D-L- myeloblastic cells. Accordingly, induction of cell surface NKG2D-L by treatment with the histone deacetylase inhibitor, valproic acid, rendered cells more sensitive to NK cytolysis. These data suggest that adoptive transfer of selected populations of alloreactive HLA-class I-mismatched NK cells in combination with pharmacological induction of NKG2D-L merit clinical evaluation as novel approaches to immunotherapy of human AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020