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Acute Non-Lymphocytic Leukemia (ANLL)

TNFα stimulates NKG2D-mediated lytic activity of acute myeloid leukemic cells

Leukemia volume 19, pages 2206–2214 (2005)Cite this article

Abstract

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 TNFα, 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 TNFα, leukemic cells may exert cytotoxicity against myeloid progenitors. This finding may have important clinical implications in the context of diseases characterized by TNFα accumulation, such as AML or myelodisplasic syndromes.

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Acknowledgements

We thank Lucie Gazel for technical helpful. This work was supported by the Association pour la Recherche contre le Cancer (ARC) (grant 4687). FG is a recipient of a grant from the Ministère de l'Education Nationale, de l'Enseignement Supérieur, et de la Recherche (MENESR).

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  1. A de Thonel

    Present address: Turku Centre for Biotechnology, Turku, Finland

Authors and Affiliations

  1. INSERMU563/CPTP, Pavillon Lefebvre Bât B, Dpt G DELSOL, Equipe G LAURENT, CHU Purpan, Toulouse, France

    F Guilloton, A de Thonel, C Jean, V Mansat-De Mas, G Laurent & A Quillet-Mary

  2. The Laboratoire d'Hématologie, Centre Hospitalier Universitaire Purpan, Toulouse, France

    V Mansat-De Mas

  3. The Service d'Hématologie, Centre Hospitalier Universitaire Purpan, Toulouse, France

    C Demur & G Laurent

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Guilloton, F., de Thonel, A., Jean, C. et al. TNFα stimulates NKG2D-mediated lytic activity of acute myeloid leukemic cells. Leukemia 19, 2206–2214 (2005). https://doi.org/10.1038/sj.leu.2403952

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