Haematologica 2003 - Supplements

4 patients had MMSET/IgH but did not overexpress FGFR3. This
finding further confirms the possible discrepancy between
MMSET/IgH positivity and FGFR3 overexpression. Comparison
between t(4;14)+ and t(4;14)- patients revealed that both groups
were well balanced with respect to the most common presenting
features of MM. In 36 patients, for whom material was available,
FISH analysis for the detection of 13q deletion and/or monosomy
was performed. Results showed that t(4;14)+ patients were more
likely to carry also del(13) than t(4;14)- patients (46% vs. 29%,
respectively). Among patients who attained stringently defined
complete remission following either Tx-1 or Tx-2, t(4;14)-
patients were 35%, as opposed to 6% of t(4;14)+ patients (p =
0.05, intention to treat). With a median follow-up of 26 months,
no difference in overall (OS) and event free survival (EFS) was
disclosed between t(4; 14)- and t(4;14)+ patients.
In summary, 27% of our MM patients carried the t(4;14). In this
cohort of homogeneously treated patients, the t(4;14) predicted
for lower response to high-dose therapy. Longer follow-up is
required to assess the influence of this abnormalities on OS and
EFS. In a subgroup of six patients carrying t(4;14), point
mutations were detected in the FGFR3 coding region, thus
suggesting a possible constitutive FGFR3 activation.
Supported by MIUR, Firb project RBAU012E9A_001 (M.Cavo),
University of Bologna, Progetti di Ricerca ex-60% (M.Cavo) and
Fondazione Carisbo.
independent of the frequency of plasma cells in the BM. Three
groups consisted of singly expressed SSX genes: SSX1, 15/70
SSX+ samples; SSX4, 11/70; SSX5, 8/70. Only SSX4 expressed
alone had any impact on survival, and in this case SSX4
expression was associated with increased survival. The remaining
group (13/70 SSX+ samples) consisted of different combinations
of two or three SSX genes expressed together and did not
correlate with survival. SSX expression was also detected in
11/40 MGUS BM samples: 7/11 SSX+ samples were SSX4+;
2/11, SSX1+; and 2/11, SSX1 and 4+. No SSX expression was
detected in uninvolved BM samples. Ongoing studies have
localized SSX expression to the CD138+/CD38+ plasma cell
population and are now focused on SSX protein detection in these
cells and anti-SSX immune responses in MM patients. This study
demonstrates that SSX expression is detectable in a significant
fraction of MM and MGUS patient BM samples, and that in MM,
expression of SSX4 alone is associated with increased survival
and co-expression of the four SSX genes correlates with reduced
survival. The relationship between SSX expression in MGUS and
progression to MM remains unclear. This work identifies SSX
genes and the proteins they encode as important new candidates
for further consideration in the study and treatment of multiple
myeloma.
052
Expression of SSX Cancer Testis Antigen Genes
Correlates with Reduced Survival in Multiple Myeloma
BJ Taylor, J Pittman, T Reiman, J Szydlowski, J Keats, AR
Belch, and LM Pilarski
Department of Oncology, University of Alberta and Cross Cancer
Institute, 11560 University Ave, Edmonton, Alberta, Canada T6G
1Z2
The identification of genes selectively expressed by malignant
cells has major implications for diagnosis, treatment, and
understanding the biology of cancer. For many different types of
cancer, the best treatment may be a combination of
chemotherapeutic and immunotherapeutic regimens, the latter
involving a vaccine consisting of tumor-specific antigens. Cancer
testis antigens (CTA) are good tumor vaccine candidates because
they are expressed in tumor and testis cells, but not normal cells.
In this study, we analyzed SSX (Synovial sarcoma, X
chromosome) CTA gene expression in Multiple Myeloma (MM)
and its corresponding pre-malignant condition, monoclonal
gammopathy of undetermined significance (MGUS). The SSX
genes comprise a family of nine members on the X chromosome.
SSX1, 2, 4, and 5 expression has been detected in many cancers,
and SYT-SSX fusion via t(X;18) is considered a central
transforming event in synovial sarcoma. In this cancer SSX may
impair the function of SYT and its interaction partner SNF/SWI,
a global transcriptional co-activator complex. From a number of
CTA assessed in preliminary experiments, SSX arose as a
favorable candidate to study in MM because SSX gene
expression was detected in MM cell lines, and in a panel of MM
and MGUS patient bone marrow (BM) samples, but not controls.
The objective of this work was to determine the frequency and
pattern of SSX gene expression in 115 MM, 45 MGUS and 12
uninvolved BM samples by nested RT-PCR. SSX expression in
MM patients was as follows: SSX1, 48/115; SSX2, 26/115;
SSX4, 43/115; SSX5, 40/115. The SSX positive samples were
arranged into five groups based on the pattern of SSX expression.
In the largest group, 23/70 SSX + samples, all 4 SSX genes were
co-expressed. This pattern correlated with reduced survival
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