title: Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells.
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.
authors.affiliation: Experimental Hematology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Langenkamp
authors.forename: Uwe
authors.initials: U
authors.lastname: Siegler
authors.forename: Simon
authors.initials: S
authors.lastname: Jörger
authors.forename: Stefan
authors.initials: S
authors.lastname: Diermayr
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kalberer
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wodnar-Filipowicz
mesh_terms: D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D055607:Receptors, Natural Killer Cell
chemical_list: D015395:Histocompatibility Antigens Class I; D055607:Receptors, Natural Killer Cell