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Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias.
Blood 2005; 105(9):3615-22Blood

Abstract

Natural killer (NK) cell-mediated cytolytic activity against tumors requires the engagement of activating NK receptors by the tumor-associated ligands. Here, we have studied the role of NKG2D and natural cytotoxicity receptors (NCRs) in the recognition of human leukemia. To detect as-yet-unknown cell-surface molecules recognized by NCRs, we developed soluble forms of NKp30, NKp44, and NKp46 as staining reagents binding the putative cognate ligands. Analysis of UL16-binding protein-1 (ULBP1), ULBP2, and ULBP3 ligands for NKG2D and of potential ligands for NKp30, NKp44, and NKp46 in healthy hematopoietic cells demonstrated the ligand-negative phenotype of bone marrow-derived CD34(+) progenitor cells and the acquisition of cell-surface ligands during the course of myeloid differentiation. In acute myeloid leukemia (AML), leukemic blasts from approximately 80% of patients expressed very low levels of ULBPs and NCR-specific ligands. Treatment with differentiation-promoting myeloid growth factors, together with interferon-gamma, upregulated cell-surface levels of ULBP1 and putative NCR ligands on AML blasts, conferring an increased sensitivity to NK cell-mediated lysis. We conclude that the ligand-negative/low phenotype in AML is a consequence of cell maturation arrest on malignant transformation and that defective expression of ligands for the activating NKG2D and NCR receptors may compromise leukemia recognition by NK cells.

Authors+Show Affiliations

Department of Research, Experimental Hematology, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15657183

Citation

Nowbakht, Pegah, et al. "Ligands for Natural Killer Cell-activating Receptors Are Expressed Upon the Maturation of Normal Myelomonocytic Cells but at Low Levels in Acute Myeloid Leukemias." Blood, vol. 105, no. 9, 2005, pp. 3615-22.
Nowbakht P, Ionescu MC, Rohner A, et al. Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. Blood. 2005;105(9):3615-22.
Nowbakht, P., Ionescu, M. C., Rohner, A., Kalberer, C. P., Rossy, E., Mori, L., ... Wodnar-Filipowicz, A. (2005). Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. Blood, 105(9), pp. 3615-22.
Nowbakht P, et al. Ligands for Natural Killer Cell-activating Receptors Are Expressed Upon the Maturation of Normal Myelomonocytic Cells but at Low Levels in Acute Myeloid Leukemias. Blood. 2005 May 1;105(9):3615-22. PubMed PMID: 15657183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. AU - Nowbakht,Pegah, AU - Ionescu,Mihai-Constantin S, AU - Rohner,Andreas, AU - Kalberer,Christian P, AU - Rossy,Emmanuel, AU - Mori,Lucia, AU - Cosman,David, AU - De Libero,Gennaro, AU - Wodnar-Filipowicz,Aleksandra, Y1 - 2005/01/18/ PY - 2005/1/20/pubmed PY - 2005/6/9/medline PY - 2005/1/20/entrez SP - 3615 EP - 22 JF - Blood JO - Blood VL - 105 IS - 9 N2 - Natural killer (NK) cell-mediated cytolytic activity against tumors requires the engagement of activating NK receptors by the tumor-associated ligands. Here, we have studied the role of NKG2D and natural cytotoxicity receptors (NCRs) in the recognition of human leukemia. To detect as-yet-unknown cell-surface molecules recognized by NCRs, we developed soluble forms of NKp30, NKp44, and NKp46 as staining reagents binding the putative cognate ligands. Analysis of UL16-binding protein-1 (ULBP1), ULBP2, and ULBP3 ligands for NKG2D and of potential ligands for NKp30, NKp44, and NKp46 in healthy hematopoietic cells demonstrated the ligand-negative phenotype of bone marrow-derived CD34(+) progenitor cells and the acquisition of cell-surface ligands during the course of myeloid differentiation. In acute myeloid leukemia (AML), leukemic blasts from approximately 80% of patients expressed very low levels of ULBPs and NCR-specific ligands. Treatment with differentiation-promoting myeloid growth factors, together with interferon-gamma, upregulated cell-surface levels of ULBP1 and putative NCR ligands on AML blasts, conferring an increased sensitivity to NK cell-mediated lysis. We conclude that the ligand-negative/low phenotype in AML is a consequence of cell maturation arrest on malignant transformation and that defective expression of ligands for the activating NKG2D and NCR receptors may compromise leukemia recognition by NK cells. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/15657183/Ligands_for_natural_killer_cell_activating_receptors_are_expressed_upon_the_maturation_of_normal_myelomonocytic_cells_but_at_low_levels_in_acute_myeloid_leukemias_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=15657183 DB - PRIME DP - Unbound Medicine ER -