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Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells

Langenkamp, Ulrich and Siegler, Uwe and Jörger, Simon and Diermayr, Stefan and Gratwohl, Alois and Kalberer, Christian P. and Wodnar-Filipowicz, Aleksandra. (2009) Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells. Haematologica : journal of hematology, Vol. 94. pp. 1590-1594.

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Official URL: http://edoc.unibas.ch/dok/A6006889

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Abstract

The concept of tumor immunosurveillance has raised prospects for natural killer cell-based immunotherapy of human cancer. The cure of acute myeloid leukemia may depend on eradication of leukemic stem cells, the self-renewing component of leukemia. Whether natural killer cells can recognize and lyse leukemic stem cells is not known. To develop strategies that effectively target acute myeloid leukemia-leukemic stem cells, we investigated anti-leukemic effects of human alloreactive single KIR(+) natural killer cells. Natural killer effectors with KIR specificity mismatched with respect to HLA class I allotype of target cells effectively recognized acute myeloid leukemia-leukemic stem cells defined phenotypically as CD34(+)CD38(-), while healthy bone marrow-derived CD34(+)CD38(-) hematopoietic stem cells were spared, as demonstrated by cytotoxicity and hematopoietic colony-forming assays. The HDAC inhibitor valproic acid increased the activating NKG2D ligand-dependent lysis of acute myeloid leukemia-CD34(+)CD38(-) leukemic stem cells. These results show that alloreactive natural killer cells have the potential to detect and target leukemic stem cells, and thus to improve the treatment outcome in acute myeloid leukemia.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Diagnostische Hämatologie (Tichelli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Diagnostische Hämatologie (Tichelli)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Hämatologie (Gratwohl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Hämatologie (Gratwohl)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel
UniBasel Contributors:Filipowicz-Wodnar, Aleksandra and Gratwohl, Alois A. and Kalberer, Christian P.A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
ISSN:0017-6567
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:10

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