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Blood, 1 January 2007, Vol. 109, No. 1, pp. 323-330. Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2005-08-027979. This Article Full Text (PDF) All Versions of this Article: blood-2005-08-027979v1 109/1/323    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fauriat, C. Articles by Costello, R. T Search for Related Content PubMed PubMed Citation Articles by Fauriat, C. Articles by Costello, R. T Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 30, 2005 Accepted July 16, 2006 Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemic cells in NCRdull phenotype induction Cyril Fauriat, Sylvaine Just-Landi, Francoise Mallet, Christine Arnoulet, Danielle Sainty, Daniel Olive, and Regis T Costello* Laboratoire d'Immunologie des Tumeurs, INSERM UMR599 Institut Paoli-Calmettes, Marseille, France Service d'Hematologie Institut Paoli-Calmettes, Marseille, France * Corresponding author; email: regis.costello{at}free.fr. NK cells play an important role in tumor cell clearance, more particularly against leukemia as shown by KIR-mismatched allogeneic stem-cell transplantation. Analysis of in vitro IL-2-expanded NK cells from patients suffering from myelo/monocytic Acute Myeloid Leukemia (AML-NK cells) has revealed poor cytolytic functions, due to deficient expression of pivotal activation molecules, i.e. the natural cytotoxicity receptors (NCR) NKp30, NKp44 and NKp46. To exclude the possibility that this observation was due to the in vitro amplification of a small NCRdull population, we performed in this study direct analysis of AML-NK phenotype without any in vitro expansion. We first confirmed that the NCRdull phenotype was not an in vitro artifact. Moreover, analysis of a large population of AML patients allowed us to demonstrate that phenotype was not restricted to a FAB subtype, and was not associated with a particular cytogenetic abnormality. Our longitudinal study of AML patients showed that the NCRdull phenotype was acquired during leukemia development since we observed its complete (for NKp46) or partial (for NKp30) reversibility in patients achieving complete remission (CR). Reversibility of the NCRdull phenotype following CR suggested that leukemic cells might be involved in NCR down-regulation. In agreement with this hypothesis, direct contact between leukemic blasts and NK cells (but not leukemia cell supernatants) induced loss or decrease in both NKp30 and NKp46 expression, while impeding NKp44 induction by IL-2. We excluded the major implication of TGF in NCR down-regulation. While the clinical anti-tumor value of NK cells is clearly demonstrated in allogeneic stem-cell transplantation, the role of NK cells in an autologous setting is not proved. Very interestingly, we observed a correlation between the NCRdull phenotype and a poor survival in AML patients, suggesting that NK deficient activation due to NCR down-regulation could play a role in patient's outcome. The prognostic value of NCR expression is discussed and pathophysiological implication of the NCR phenotype will be further investigated in a larger study. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. Szczepanski, M. Szajnik, M. Czystowska, M. Mandapathil, L. Strauss, A. Welsh, K. A. Foon, T. L. Whiteside, and M. Boyiadzis Increased Frequency and Suppression by Regulatory T Cells in Patients with Acute Myelogenous Leukemia Clin. Cancer Res., May 15, 2009; 15(10): 3325 - 3332. [Abstract] [Full Text] [PDF] C. Menard, J.-Y. Blay, C. Borg, S. Michiels, F. Ghiringhelli, C. Robert, C. Nonn, N. Chaput, J. Taieb, N. F. Delahaye, et al. Natural Killer Cell IFN-{gamma} Levels Predict Long-term Survival with Imatinib Mesylate Therapy in Gastrointestinal Stromal Tumor-Bearing Patients Cancer Res., April 15, 2009; 69(8): 3563 - 3569. [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] Y. M. El-Sherbiny, J. L. Meade, T. D. Holmes, D. McGonagle, S. L. Mackie, A. W. Morgan, G. Cook, S. Feyler, S. J. Richards, F. E. Davies, et al. The Requirement for DNAM-1, NKG2D, and NKp46 in the Natural Killer Cell-Mediated Killing of Myeloma Cells Cancer Res., September 15, 2007; 67(18): 8444 - 8449. [Abstract] [Full Text] [PDF]

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