Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies

• Published in: Blood 2003-02, Vol.101 (3), p.955-960
• Main Authors: Wang, Zhiqing, Zhang, Yana, Liu, Haichao, Salati, Emanuela, Chiriva-Internati, Maurizio, Lim, Seah H.
• Format: Article
• Language: English
• Subjects: Antibodies, Neoplasm - blood; Antibody Formation; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic agents; Biological and medical sciences; Case-Control Studies; Gene Expression; Hematologic and hematopoietic diseases; Hematologic Neoplasms - immunology; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - pathology; Humans; Immunoglobulin G - blood; Immunotherapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Multiple Myeloma - immunology; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Nuclear Proteins - genetics; Nuclear Proteins - immunology; Nuclear Proteins - metabolism; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - analysis; Tissue Distribution
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-06-1930

Recent studies in tumor immunology indicate that malignant cells frequently express normal testicular-specific proteins. Because these proteins show restricted normal tissue distribution, they are usually highly immunogenic and may be potential targets for immunotherapy. In the present study, we have used a pair of sequence-specific primers in reverse transcription–polymerase chain reaction (RT-PCR) and sequence analysis to demonstrate that the X-linked gene encoding SPAN-Xb is expressed in multiple myeloma and other hematologic malignancies such as chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML). RT-PCR analysis demonstrates that SPAN-Xb is a cancer/testis antigen and shows a restricted normal tissue expression. It is not expressed in any normal tissue except testis. SPAN-Xb recombinant protein was produced and used in enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. High-titer immunoglobulin G (IgG) antibodies, of IgG3 or IgG2 subclass, against SPAN-Xb were detectable in the sera of these patients. In contrast, SPAN-Xb mRNA or antibodies could not be detected in any of the healthy donors. There was a good correlation betweenSPAN-Xb gene expression and B-cell immune responses. These results suggest the in vivo immunogenicity of the SPAN-Xb protein. The presence of high-titer IgG responses suggests that the B-cell responses are likely to have been generated with CD4 T-cell cognitive help. Based on these data, we conclude that SPAN-Xb is a novel member of the family of cancer/testis antigens aberrantly expressed by, and capable of inducing, immune responses in patients with multiple myeloma and other hematologic malignancies.