title: NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML.
abstract: Natural killer cells have been shown to be relevant in the recognition and lysis of acute myeloid leukemia. In childhood acute lymphoblastic leukemia, it was shown that HLA I expression and KIR receptor-ligand mismatch significantly impact ALL cytolysis. We characterized 14 different primary childhood AML blasts by flow cytometry including NKG2D ligands. Further HLA I typing of blasts was performed and HLA I on the AML blasts was quantified. In two healthy volunteer NK cell donors HLA I typing and KIR genotyping were done. Blasts with high NKG2D ligand expression had significantly higher lysis by isolated NK cells. Grouping the blasts by NKG2D ligand expression led to a significant inverse correlation of HLA I expression and cytolysis in NKG2D low blasts. Furthermore, a significant positive correlation of NKG2D ligand expression and blast cytolysis was shown. No impact of KIR ligand-ligand mismatch was found but a significantly increased lysis of homozygous C2 blasts by KIR2DL1 negative NK cells (donor B) was revealed. In conclusion, NKG2D signaling leads to NK cell mediated lysis of childhood AML despite high HLA I expression.
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ditthard
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Mezger
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michaelis
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfeiffer
mesh_terms: D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000097625:HLA-E Antigens; C527085:KLRK1 protein, human