Molecular persistence of chronic myeloid leukemia caused by donor T cells specific for lineage-restricted maturation antigens not recognizing immature progenitor-cells

Leukemia
P A von dem BorneJ H Frederik Falkenburg

Abstract

Although donor lymphocyte infusion (DLI) induces complete remissions in 70% of patients with relapsed chronic myeloid leukemia (CML) after allogeneic stem-cell transplantation (SCT), some patients are refractory to DLI by showing disease persistence. In a patient who received DLI for relapsed CML, we observed persisting molecular disease despite a hematological and cytogenetic remission in the absence of graft-versus-host disease (GVHD). To determine the nature of this immune response, we isolated leukemia-reactive donor T-cell clones from the bone marrow (BM) of the patient at the time of clinical response. Four different types of CD8+ HLA class I restricted T-cell clones were obtained that were cytotoxic against Ebstein-Barr virus-transformed B-cell lines (EBV-LCL) of the patient, but not the donor, indicating recognition of minor histocompatibility antigens (mHags). By using survival studies with CFSE labelled BM cells populations, a hematopoietic progenitor cell inhibition assay and direct morphological examination we showed that the T-cell clones recognized mature monocytic and myeloid cells, whereas immature BM progenitor cells were insufficiently lysed. This patient's refractoriness for DLI appears to be caused by inadeq...Continue Reading

References

Feb 1, 1986·Annals of Internal Medicine·E D ThomasK Doney
Jan 20, 1999·The Journal of Experimental Medicine·H DolstraE van de Wiel-van Kemenade
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E H WarrenS R Riddell
Jan 10, 2001·The Journal of Experimental Medicine·A G BricknerS R Riddell
Nov 2, 2001·Nature·T ReyaI L Weissman
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·W A Erik MarijtJ H Frederik Falkenburg
May 14, 2003·The Journal of Experimental Medicine·Makoto MurataStanley R Riddell
May 29, 2003·The Journal of Experimental Medicine·Yoshiki AkatsukaToshitada Takahashi
Sep 6, 2003·Methods : a Companion to Methods in Enzymology·M A W G van der HoornJ H F Falkenburg
Sep 10, 2003·Experimental Hematology·J H Frederik FalkenburgRoel Willemze
Nov 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroki TorikaiToshitada Takahashi

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Citations

Jan 29, 2011·Expert Opinion on Biological Therapy·Claire Roddie, Karl S Peggs
Nov 12, 2010·Cytotherapy·Jan Joseph Melenhorst, Austin John Barrett
Apr 4, 2008·Cancer Letters·Bruno Quesnel
Mar 21, 2007·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Theresia M WestersArjan A van de Loosdrecht
Oct 7, 2008·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Bruno Quesnel
Feb 21, 2008·European Journal of Haematology·Jochen Greiner, Michael Schmitt
Jul 29, 2006·Springer Seminars in Immunopathology·Jocelyne DemengeotAntónio Coutinho

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