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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 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 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 Fauriat, C. Articles by Costello, R. T. Search for Related Content PubMed PubMed Citation Articles by Fauriat, C. Articles by Costello, R. T. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction Cyril Fauriat1, Sylvaine Just-Landi1, Françoise Mallet1, Christine Arnoulet2, Danielle Sainty2,3, Daniel Olive1,3, and Regis T. Costello1,3,4, 1 Laboratoire d'Immunologie des Tumeurs, Institut National de la Santé et de la Recherche Médicale (INSERM) Unite Mixté de Recherche (UMR) 599, and 2 Service d'Hématologie, Institut Paoli-Calmettes, Marseille, France; 3 Faculté de Médecine de Marseille, Marseille, France; and 4 Service d'Hématologie, Hôpital Nord, Marseille, France. Natural killer (NK) cells play an important role in tumor-cell clearance, particularly against leukemia, as shown by killer cell inhibitory receptor (KIR)–mismatched allogeneic stem cell transplantation. Analysis of in vitro IL-2–expanded NK cells from patients with myelocytic/monocytic acute myeloid leukemia (AML-NK cells) has revealed poor cytolytic functions because of deficient expression of pivotal activation molecules—the natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46. To exclude the possibility that this observation was caused by the in vitro amplification of a small NCRdull population, we analyzed the AML-NK phenotype directly, 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 French-American-British (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 because we observed its complete (for NKp46) or partial (for NKp30) reversibility in patients achieving complete remission (CR). Reversibility of the NCRdull phenotype after CR suggested that leukemia 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 NKp30 and NKp46 expression while impeding NKp44 induction by IL-2. We excluded the major implication of TGF-ß in NCR down-regulation. Although the clinical antitumor value of NK cells is clearly demonstrated in allogeneic stem cell transplantation, the role of NK cells in autologous transplantation is not proved. Interestingly, we observed a correlation between the NCRdull phenotype and poor survival in AML patients, suggesting that NK-deficient activation caused by NCR down-regulation could play a role in patient outcome. The prognostic value of NCR expression is discussed, and pathophysiologic 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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