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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-06-1930.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 955-960
IMMUNOBIOLOGY
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
From the Division of Hematology and Oncology, Texas
Tech University Health Sciences Center, Amarillo; and Biotherapy and
Stem Cell Transplant Program, Don and Sybil Harrington Cancer Center,
Amarillo, TX.
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 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 patients
with multiple myeloma and other hematologic malignancies.
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