Researchers have been exploring the use of cytogenetic studies
to identify patients with myeloma who may have poor prognoses. However, because
of the low proliferative activity in myeloma, conventional cytogenetic studies
requiring metaphase spreads are difficult. The tests may have to be performed
repeatedly to obtain results.
Fluorescent in situ hybridization (FISH) is a powerful adjunct
to traditional G-banding because it allows the identification of abnormal
clones in interphase nuclei and cryptic translocations in metaphase cells,
independent of the proliferative capacity of the tumor cells. A number of
studies have shown a correlation between monosomy or deletion of chromosome
13 and poor prognosis in multiple myeloma.1,2
The biologic significance of monosomy 13 or deletion 13q (-13/13q-)
aberrations is not understood. The Rb gene maps to 13q14 and is the prototype
for the tumor suppressor gene model.3 The Rb gene product has been shown to
suppress tumorigenesis in neoplastic cell lines, inhibit apoptosis, and facilitate
differentiation. In myeloma, Rb is believed to downregulate IL-6 gene expression
(IL-6 is an important growth factor in myeloma).
Patients with poor prognoses should be selected for more aggressive
therapy, although there is no treatment strategy (including novel agents)
that has shown good results with high-risk disease. Because of the poor results
with even aggressive high-dose therapy in chromosome deletion 13 myeloma,
some people advocate that such patients not be considered candidates for high
dose therapy. However, even though the results with high-dose therapy are
poor in these cases, they may be the best possible response for this group
of patients. Hence, it can be argued that if high-dose therapy offers better
results after alternative therapies, these patients should not be denied access
to high-dose therapy.
An interesting aspect of the prognostic significance of chromosome 13 abnormalities
in multiple myeloma is the impact of the cytogenetic technique used to detect
the anomaly.4,5 Traditional G-banding techniques are being suggested, because
they enable detection of chromosome 13 abnormalities in the most proliferative
sub-clone, that is most relevant to prognosis. When the same anomaly is
detected by FISH, it tends to not have the same prognostic significance
in statistical analyses.
1. Barlogie B, Sawyer J, Ayers D, et al. Chromosome 13 myeloma
is a distinct entity with poor prognosis despite tandem autotransplants. Blood.
2. Seong C, Delasalle K, Hayes K, et al. Prognostic value of
cytogenetics in multiple myeloma. Br J Haematol. 1998; 101:189-195.
3. Juge-Morineau N, Harousseau JL, Amiot M, Bataille R. The
retinoblastoma susceptibility gene RB-1 in multiple myeloma. Leukemia Lymphoma.
4. Shaughnessy J, Barlogie B, McCoy J et al. Early relapse after
total therapy II for multiple myeloma (MM) is significantly associated with
cytogenetic abnormalities of chromosome 13 (CA13) but not interphase FISH-del
13 or plasma cell labeling index (PCLI). Blood. 2001; 98:734A.
5. Debes Marun C, Bailey R, Dewald G et al. In multiple myeloma
the combination of an elevated plasma cell labeling index (PCLI) and chromosome
13 deletion, detected by interphase FISH, can identify patients with chromosome
13 abnormalities detected by karyotype. Blood. 2001; 98:156A