Antibody Responses Associated with the Graft-versus-Leukemia Effect in Adult T-Cell Leukemia

Abstract

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATL, especially the acute and lymphoma subtypes, is poor with conventional and high-dose chemotherapy. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATL has been reported, suggesting the presence of a graft-versus-leukemia (GVL) effect against this malignancy. To identify the target antigens associated with tumor rejection, we used SEREX (serological identification of antigens by recombinant cDNA expression cloning) to screen ATL complementary DNA expression libraries with sera from an ATL patient who had a GVL response after allo-HSCT. Among the isolated clones, autocrine motility factor receptor (AMFR), which encodes a glycosylated transmembrane protein, was found to have selective reactivity with the sera obtained during tumor regression. Real-time reverse transcription polymerase chain reaction analysis for AMFR showed highest expression in the testis among normal tissues. Furthermore, aberrant AMFR expression was found in at least some ATL patients. Taken together, these findings suggest that AMFR may be one of the GVL antigens that provoke effective antitumor immunity against ATL in allogeneic settings.