TNFalpha stimulates NKG2D-mediated lytic activity of acute myeloid leukemic cells.
Leukemia
; 19(12): 2206-14, 2005 Dec.
Article
en En
| MEDLINE
| ID: mdl-16239914
The mechanism by which leukemic cells interfere with normal hematopoiesis remains unclear. We show here that, whereas the leukemic KG1a cells are naturally devoid from cellular cytotoxicity, once activated by TNFalpha, they display cytolytic activity toward various cellular targets including CFU-GM. This mechanism is dependent on stimulation of the granzyme B/perforin system. In addition, KG1a cells expressed the NKG2D receptor and its signal-transducing adaptator DAP 10, which were functional as confirmed by redirected lysis experiments. Interestingly, flow cytometry analysis of 20 samples of patients with acute myeloid leukemia (AML) (FAB M0-M5) revealed the expression of NKG2D (40%) and other natural cytotoxicity receptors (40% for NKp30, 74% for NKp44, 39% for NKp46) by a pool >15% of leukemic cells. Furthermore, CD34+ hematopoietic progenitors undergoing granulomonocytic differentiation expressed NKG2D ligands. Altogether, we propose a model in which, upon stimulation by TNFalpha, leukemic cells may exert cytotoxicity against myeloid progenitors. This finding may have important clinical implications in the context of diseases characterized by TNFalpha accumulation, such as AML or myelodisplasic syndromes.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Inmunológicos
/
Leucemia Mieloide
/
Factor de Necrosis Tumoral alfa
/
Células Progenitoras Mieloides
/
Citotoxicidad Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido