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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-06-1930.
Submitted July 1, 2002
Accepted August 13, 2002
Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies
Zhiqing Wang, Yana Zhang, Haichao Liu, Emanuela Salati, Maurizio Chiriva-Internati, and Seah H Lim*
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo, Texas, USA; Biotherapy and Stem Cell Transplant, Harrington Cancer Center, Amarillo, Texas, USA
* Corresponding author; email: slim{at}harringtoncc.org.
Recent works in tumor immunology indicate that malignant cells frequently express normal testicular-specific proteins. Since these proteins show a very 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 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 CLL, CML and AML. By RT-PCR analysis, SPAN-Xb is a cancer-testis antigen and shows a very restricted normal tissue expression. It is not expressed in any normal tissue, except normal testis. SPAN-Xb recombinant protein was produced and used in ELISA and Western blot analysis. High titer 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 between SPAN-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 vivo in patients with multiple myeloma and other hematologic malignancies.
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