|
|
Blood, 1 May 2004, Vol. 103, No. 9, pp. 3431-3439.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-02-0400.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes
Pearlie Kay Epling-Burnette,
Jeffrey S. Painter,
Pratima Chaurasia,
Fanqi Bai,
Sheng Wei,
Julie Y. Djeu, and
Thomas P. Loughran, Jr
From the Hematologic Malignancy and Immunology Programs, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL; James A. Haley Veterans' Administration Hospital, Tampa, FL; and Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA.
The natural killer (NK) type of lymphoproliferative disease of granular lymphocytes (LDGL) is associated with the expansion of CD3-, CD16+, and/or CD56+ lymphocytes. We have examined the repertoire of NK receptors expressed on these cells and delineated the functional activity. We found skewed NK receptor expression on patient NK cells. Reactivity to a single anti-killer cell immunoglobulin-like receptor (anti-KIR) antibody was noted in 7 of 13 patients. LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA. In contrast, CD94 and its inhibitory heterodimerization partner NKG2A were homogenously expressed at high levels on these NK cells. Interestingly, these patients expressed a large number of activating KIR receptors by genotype analysis. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that lower than normal levels of RNA of the inhibitory KIR was present in some patients in contrast to normal NK cells. Consistent with a high level of activating receptors, we found the NK-LDGL cells have potent cytolytic function in both direct and redirected cytotoxicity assays. These results demonstrate that patients with NK-LDGL have an increased activating-to-inhibitory KIR ratio. This altered ratio might induce inappropriate lysis or cytokine production and impact the disease pathogenesis. (Blood. 2004;103:3431-3439)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. K. Epling-Burnette, L. Sokol, X. Chen, F. Bai, J. Zhou, M. A. Blaskovich, J. Zou, J. S. Painter, T. D. Edwards, L. Moscinski, et al.
Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling
Blood,
December 1, 2008;
112(12):
4694 - 4698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Thomas, J. K. Haseman, J. I. Goodman, J. M. Ward, T. P. Loughran Jr, and P. J. Spencer
A Review of Large Granular Lymphocytic Leukemia in Fischer 344 Rats as an Initial Step Toward Evaluating the Implication of the Endpoint to Human Cancer Risk Assessment
Toxicol. Sci.,
September 1, 2007;
99(1):
3 - 19.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Boudewijns, J. J.M. van Dongen, and A. W. Langerak
The Human Androgen Receptor X-Chromosome Inactivation Assay for Clonality Diagnostics of Natural Killer Cell Proliferations
J. Mol. Diagn.,
July 1, 2007;
9(3):
337 - 344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. K. Epling-Burnette, F. Bai, J. S. Painter, D. E. Rollison, H. R. Salih, M. Krusch, J. Zou, E. Ku, B. Zhong, D. Boulware, et al.
Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors
Blood,
June 1, 2007;
109(11):
4816 - 4824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Sokol and T. P. Loughran Jr.
Large granular lymphocyte leukemia.
Oncologist,
March 1, 2006;
11(3):
263 - 273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zambello, T. Berno, G. Cannas, I. Baesso, G. Binotto, E. Bonoldi, P. Bevilacqua, M. Miorin, M. Facco, L. Trentin, et al.
Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)
Blood,
December 1, 2005;
106(12):
3926 - 3931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.K. Epling-Burnette, F. Bai, J. S. Painter, and T. P. Loughran
In Addition to Immune Suppression, There Is Defective Maturation of CD34+ Cells in Patients with Natural Killer-Lymphoproliferative Disease of Granular Lymphcoytes (NK-LDGL).
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
2404 - 2404.
[Abstract]
|
|
|
|
|
|
|
A. P. Williams, A. R. Bateman, and S. I. Khakoo
HANGING IN THE BALANCE: KIR and Their Role in Disease
Mol. Interv.,
August 1, 2005;
5(4):
226 - 240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.K. Epling-Burnette, F. Bai, J. S. Painter, S. Wei, J. Y. Djeu, and T. P. Loughran
Reduced Inhibitory KIR Receptors in Patients with NK-Lymphoproliferative Disease of Large Granular Lymphocytes (NK-LDGL) Leads to Dysregulated Killing.
Blood (ASH Annual Meeting Abstracts),
November 16, 2004;
104(11):
2661 - 2661.
[Abstract]
|
|
|
|
|
