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* Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany; and
Institute of Immunology, University Hospital of Essen, Essen, Germany
Killer Ig-like receptors (KIR) and HLA class I ligands were studied in unrelated hemopoietic stem cell transplantation for chronic myeloid leukemia (n = 108). Significantly improved overall survival was observed in patients, which were homozygous for HLA-C-encoded group 1 (C1) ligands compared with those with group 2 (C2) ligands. Favorable outcome in the former patient group was an early effect that was highly significant in patients transplanted with G-CSF-mobilized peripheral blood and patients with advanced disease stages. In contrast, presence of C1 ligands in the donor was associated with significantly reduced patient survival. The differential roles of the two HLA-C ligands are explained in the context of a biased NK cell reconstitution, which is generally dominated by the presence of C1- but absence of C2-specific NK cells. The clinical observations are corroborated by in vitro experiments showing that NK cells derived from hemopoietic progenitor cells generally acquire the C1-specific inhibitory KIR2DL2/3 at earlier time points and with higher frequency than the C2-specific KIR2DL1. These findings define a novel determinant for understanding the role of NK cells in clinical hemopoietic stem cell transplantation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Deutsche Krebshilfe (to P.W. and M.U.) within the Research Network "Immune Therapy of Malignant Disease by Transplantation of Allogeneic Hematopoietic Stem Cells."
2 Address correspondence and reprint requests to Dr. Markus Uhrberg, Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Düsseldorf, Building 14.80, Moorenstrasse 5, D-40225 Düsseldorf, Germany. E-mail address: uhrberg{at}itz.uni-duesseldorf.de
3 Abbreviations used in this paper: HSCT, hemopoietic stem cell transplantation; KIR, killer cell Ig-like receptor; aGvHD, acute graft-vs-host disease; SSP, sequence-specific primer; RR, risk ratio; CI, confidence interval; OS, overall survival; EFS, event-free survival; TRM, transplantation-related mortality; PBSC, peripheral blood stem cell; BM, bone marrow; CML, chronic myeloid leukemia; NCAM, neural cell adhesion molecule.
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