title: Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation.
abstract: Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8(+) T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p < 0.01). Increment of WT1 transcripts eventually resulted in relapse and subsequent death of the patients. In patients with longer survival and continuous complete remission (cCR) after SCT, higher and enduring frequencies of WT1-specific CTL than in patients developing a relapse were detected. These cells were effector T cells secreting interferon gamma and granzyme B. In summary, WT1 is a suitable marker for the detection of minimal residual disease after SCT or chemotherapy. A rising WT1 signal correlated with a dismal prognosis of the patients. WT1-specific CD8(+) T cells might contribute to the maintenance of a cCR. Targeting WT-1 by peptide/protein vaccination as well as adoptive transfer of genetically modified T cells are future options in the individualized therapy for AML/MDS patients.
authors.affiliation: Department of Internal Medicine III, University of Rostock, Rostock, Germany.|Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Rosaely
authors.initials: R
authors.lastname: Casalegno-Garduño
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, University of Rostock, Rostock, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Spitschak
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine III, University of Rostock, Rostock, Germany.|Department of Hematology/Oncology, Jena University Hospital, Jena, Germany.
authors.forename: Inken
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: Department of Internal Medicine C, Hematology/Oncology, University of Greifswald, Greifswald, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hirt
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine III, University of Rostock, Rostock, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000628:therapy; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D025721:WT1 Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: AML; MDS; WT1; specific T cells