Kuebler, Ayline and Woiterski, Jeanette and Witte, Kai-Erik and Buehring, Hans-Joerg and Hartwig, Udo F. and Ebinger, Martin and Oevermann, Lena and Mezger, Markus and Herr, Wolfgang and Lang, Peter and Handgretinger, Rupert and Muenz, Christian and Andre, Maya C. (2014) Both mature KIR+ and immature KIR- NK cells control pediatric acute B-cell precursor leukemia in NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz mice. BLOOD, 124 (26). pp. 3914-3923. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Therapeutic natural killer (NK)-cell-mediated alloreactivity toward acute myeloid leukemia has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B-cell precursor leukemia (BCP-ALL) appears to be resistant to NK-cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. In this study, we demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity toward pediatric BCP-ALL in vivo. Notably, both adoptively transferred mature KIR+ NK cells and immature KIR- NK cells arising early posttransplantation in humanized NSG mice exerted substantial antileukemic activity. Low-dose and long-term treatment of humanized NSG mice with the DNA-demethylating agent 5-aza-cytidine distinctly enhanced the antitumor response, interestingly without inducing common inhibitory KIR expression but rather by promoting the differentiation of various NK-cell precursor subsets. Collectively, these data indicate that the future design of innovative therapy protocols should consider further exploitation of NK-cell-mediated immune responses for poor prognosis pediatric BCP-ALL patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELL; DIFFERENTIATION IN-VIVO; ACUTE MYELOID-LEUKEMIA; LOW-DOSE AZACITIDINE; INHIBITORY RECEPTORS; CYTOLYTIC ACTIVITY; DNA METHYLATION; MEDIATED LYSIS; T-CELL; TRANSPLANTATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Aug 2019 09:13 |
| Last Modified: | 05 Aug 2019 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9043 |
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