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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 (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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 21, 2006 Accepted February 12, 2007 Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors P K Epling-Burnette*, Fanqi Bai, Jeffrey S. Painter, Dana Rollison, Helmut R Salih, Matthias Krusch, JianXiang Zou, Edna Ku, Bin Zhong, David Boulware, Lynn Moscinski, Sheng Wei, Julie Y. Djeu, and Alan F. List James A. Haley VA Hospital, Tampa, FL, United States Immunology Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, Tampa, FL, United States Department of Internal Medicine II, University Hospital, Eberhard-Karls-University, Tuebingen, Germany Hematologic Malignancy Division, H. Lee Moffitt Cancer Center, Tampa, FL, United States Biostatistics Program, H. Lee Moffitt Cancer Center, Tampa, FL, United States Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL, United States * Corresponding author; email: pearlie.burnette{at}moffitt.org. 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 normal donors and found reduced activity in the patient population (K562 cytolysis, 19% ± 21 S.D. vs. 40% ± 17) (p<0.001). NK cytotoxicity in MDS patients was reduced against three 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=0.01), abnormal karyotype (p=0.05), the presence of excess blasts (p=0.01), and age-adjusted bone marrow hypercellularity (p=0.04). MDS patients had reduced display of the activating receptor NKp30 and NKG2D downregulation closely correlated with impaired NK function (p=0.001). NKG2D ligands (MICA/B) were expression 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?

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