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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 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 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 Diermayr, S. Articles by Wodnar-Filipowicz, A. Search for Related Content PubMed PubMed Citation Articles by Diermayr, S. Articles by Wodnar-Filipowicz, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 Diermayr1, Heike Himmelreich1, Bojana Durovic1, Arina Mathys-Schneeberger1, Uwe Siegler1,2, Ulrich Langenkamp1, Jan Hofsteenge2, Alois Gratwohl3, André Tichelli3, Monika Paluszewska4, Wieslaw Wiktor-Jedrzejczak4, Christian P. Kalberer1, and Aleksandra Wodnar-Filipowicz1 1 Department of Research, University Hospital Basel, Basel, Switzerland; 2 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; 3 Stem Cell Transplant Team, University Hospital Basel, Basel, Switzerland; and 4 Department of Hematology and Oncology, Medical University of Warsaw, Warsaw, Poland 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 major human leukocyte antigen (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 analyzed. NKG2D-L were selectively expressed on monoblastic cells in AML M4 and M5 yet absent or weakly expressed on myeloblastic cells in all AML subtypes. Paucity of cell-surface NKG2D-L was not the result of shedding because levels of soluble ULBP1 ligand measured in AML plasma were in the 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 pharmacologic induction of NKG2D-L merits clinical evaluation as novel approaches to immunotherapy of human AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Schrump Cytotoxicity Mediated by Histone Deacetylase Inhibitors in Cancer Cells: Mechanisms and Potential Clinical Implications Clin. Cancer Res., June 15, 2009; 15(12): 3947 - 3957. [Abstract] [Full Text] [PDF] C. Cerboni, M. Ardolino, A. Santoni, and A. Zingoni Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells Blood, March 26, 2009; 113(13): 2955 - 2964. [Abstract] [Full Text] [PDF]

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