Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia

The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relap sed chronic myelogenous leukemia (CML) after allogeneic bone marrow transpl antation 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 remissio n after infusion of donor T cells. Sera from these individuals recognized 1 3 distinct gene products represented in a CML-derived cDNA library. Two pro teins, J kappa-recombination signal-binding protein (RBP-J kappa) and relat ed adhesion focal tyrosine kinase (RAFTK), were recognized by sera from thr ee of 19 DLI responders. None of these antigens were recognized by sera fro m healthy donors or patients with chronic graft-versus-host disease. Four g ene products were recognized by sera from CML patients treated with hydroxy urea and nine were detected by sera from CML patients who responded to IFN- a. Antibody titers specific for RAFTK, but not for RBP-JK, 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-cel l immunity. The characterization of B cell-defined antigens may help identi fy clinically relevant targets of the GVL response in vivo.