NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML

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 childho...

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Main Authors: Patrick Schlegel, Kerstin Ditthard, Peter Lang, Markus Mezger, Sebastian Michaelis, Rupert Handgretinger, Matthias Pfeiffer
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/473175
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author Patrick Schlegel
Kerstin Ditthard
Peter Lang
Markus Mezger
Sebastian Michaelis
Rupert Handgretinger
Matthias Pfeiffer
author_facet Patrick Schlegel
Kerstin Ditthard
Peter Lang
Markus Mezger
Sebastian Michaelis
Rupert Handgretinger
Matthias Pfeiffer
author_sort Patrick Schlegel
collection DOAJ
description 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.
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spelling doaj-art-d6f6007238ea4bf884ce03e9fd6db61e2025-02-03T07:24:38ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/473175473175NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AMLPatrick Schlegel0Kerstin Ditthard1Peter Lang2Markus Mezger3Sebastian Michaelis4Rupert Handgretinger5Matthias Pfeiffer6Department of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyDepartment of Hematology and Oncology, University Children’s Hospital Tübingen, University of Tübingen, Hoppe-Seyler-Straße 1, 72076 Tübingen, GermanyNatural 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.http://dx.doi.org/10.1155/2015/473175
spellingShingle Patrick Schlegel
Kerstin Ditthard
Peter Lang
Markus Mezger
Sebastian Michaelis
Rupert Handgretinger
Matthias Pfeiffer
NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
Journal of Immunology Research
title NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
title_full NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
title_fullStr NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
title_full_unstemmed NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
title_short NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML
title_sort nkg2d signaling leads to nk cell mediated lysis of childhood aml
url http://dx.doi.org/10.1155/2015/473175
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