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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4816-4824. Prepublished online as a Blood First Edition Paper on March 6, 2007; DOI 10.1182/blood-2006-07-035519. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-07-035519v1 109/11/4816    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 Epling-Burnette, P. K. Articles by List, A. F. Search for Related Content PubMed PubMed Citation Articles by Epling-Burnette, P. K. Articles by List, A. F. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors Pearlie K. Epling-Burnette1,4, Fanqi Bai1, Jeffrey S. Painter1, Dana E. Rollison5, Helmut R. Salih6, Matthias Krusch6, JianXiang Zou1, Edna Ku2, Bin Zhong1, David Boulware7, Lynn Moscinski4, Sheng Wei1, Julie Y. Djeu1,4, and Alan F. List2,4 1 Immunology Program H. Lee Moffitt Cancer Center, Tampa, FL; 2 Hematologic Malignancy Division, H. Lee Moffitt Cancer Center, Tampa, FL; 3 James A. Haley Veterans Administration (VA) Hospital, Tampa, FL; 4 Department of Interdisciplinary Oncology, University of South Florida, Tampa; 5 Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, Tampa, FL; 6 Department of Internal Medicine II, University Hospital, Eberhard-Karls-University, Tübingen, Germany; 7 Biostatistics Program, H. Lee Moffitt Cancer Center, Tampa, FL Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis with potential for progression to acute myeloid leukemia (AML). We compared natural killer (NK) cytolytic function in 48 MDS patients with 37 healthy donors and found reduced activity in the patient population (K562 cytolysis, 19% ± 21% SD versus 40% ± 17%) (P < .001). NK cytotoxicity in MDS patients was reduced against 3 disparate tumor targets with differential activating receptor requirement, suggesting global defects in NK function. Reduced NK function in MDS was significantly associated with higher International Prognostic Score (P = .01), abnormal karyotype (P = .05), the presence of excess blasts (P = .01), and age-adjusted bone marrow hypercellularity (P = .04). MDS patients had a display of the activating receptor NKp30, and NKG2D down-regulation closely correlated with impaired NK function (P = .001). NKG2D ligands (MICA and MICB) were expressed on CD34+ cells from bone marrow of 30% of MDS patients and a leukemic cell line derived from an MDS patient (MDS1). Collectively, these findings suggest that impairment of NK cytolytic function derives in part from reduced activating NK receptors such as NKG2D in association with disease progression. Evasion of NK immunosurveillance may have importance for MDS disease progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Crane, S. J. Han, J. J. Barry, B. J. Ahn, L. L. Lanier, and A. T. Parsa TGF-{beta} downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients Neuro Oncology, November 5, 2009; (2009) nop009v1. [Abstract] [Full Text] [PDF] M. E.D. Chamuleau, T. M. Westers, L. van Dreunen, J. Groenland, A. Zevenbergen, C. M. Eeltink, G. J. Ossenkoppele, and A. A. van de Loosdrecht Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome Haematologica, April 1, 2009; 94(4): 496 - 506. [Abstract] [Full Text] [PDF] N. Nausch, I. E. Galani, E. Schlecker, and A. Cerwenka Mononuclear myeloid-derived "suppressor" cells express RAE-1 and activate natural killer cells Blood, November 15, 2008; 112(10): 4080 - 4089. [Abstract] [Full Text] [PDF]

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