title: Antibodies specifically target AML antigen NuSAP1 after allogeneic bone marrow transplantation.
abstract: Identifying the targets of immune response after allogeneic hematopoietic cell transplantation (HCT) promises to provide relevant immune therapy candidate proteins. We used protein microarrays to serologically identify nucleolar and spindle-associated protein 1 (NuSAP1) and chromatin assembly factor 1, subunit B (p60; CHAF1b) as targets of new antibody responses that developed after allogeneic HCT. Western blots and enzyme-linked immunosorbent assays (ELISA) validated their post-HCT recognition and enabled ELISA testing of 120 other patients with various malignancies who underwent allo-HCT. CHAF1b-specific antibodies were predominantly detected in patients with acute myeloid leukemia (AML), whereas NuSAP1-specific antibodies were exclusively detected in patients with AML 1 year after transplantation (P < .001). Complete genomic exon sequencing failed to identify a nonsynonymous single nucleotide polymorphism (SNP) for NuSAP1 and CHAF1b between the donor and recipient cells. Expression profiles and reverse transcriptase-polymerase chain reaction (RT-PCR) showed NuSAP1 was predominately expressed in the bone marrow CD34(+)CD90(+) hematopoietic stem cells, leukemic cell lines, and B lymphoblasts compared with other tissues or cells. Thus, NuSAP1 is recognized as an immunogenic antigen in 65% of patients with AML following allogeneic HCT and suggests a tumor antigen role.
authors.affiliation: Department of Medicine, Stanford University Medical Center, CA 94305-5623, USA.
authors.forename: Persis P
authors.initials: PP
authors.lastname: Wadia
authors.forename: Marc
authors.initials: M
authors.lastname: Coram
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Armstrong
authors.forename: Michael
authors.initials: M
authors.lastname: Mindrinos
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D008875:Middle Aged; D014184:Transplantation, Homologous; D054928:Validation Studies as Topic; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human