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): 3615-22, 2005 May 01.
Article
en En
| MEDLINE
| ID: mdl-15657183
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Monocitos
/
Receptores Inmunológicos
/
Leucemia Mieloide
/
Regulación Neoplásica de la Expresión Génica
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2005
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Estados Unidos