title: Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia.
abstract: The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, Jkappa-recombination signal-binding protein (RBP-Jkappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-alpha. Antibody titers specific for RAFTK, but not for RBP-Jkappa, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo.
authors.affiliation: Center for Hematologic Oncology, and. Department of Biostatistical Science, Dana-Farber Cancer Institute, and. Department of Medicine, and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wu
authors.forename: X F
authors.initials: XF
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: McLaughlin
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: C
authors.initials: C
authors.lastname: Canning
authors.forename: B
authors.initials: B
authors.lastname: Stein
authors.forename: E P
authors.initials: EP
authors.lastname: Alyea
authors.forename: R J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: G
authors.initials: G
authors.lastname: Dranoff
authors.forename: J
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D051418:Focal Adhesion Kinase 2; D015723:Gene Library; D020544:Graft vs Leukemia Effect; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D012074:Remission Induction; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2