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Significance of Chromosome 13 Deletions in Multiple Myeloma: Seema Singhal, MD
08.08.02

 

Significance of Chromosome 13 Deletions in Multiple Myeloma: Seema Singhal, MD

 

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.

 

References

1. Barlogie B, Sawyer J, Ayers D, et al. Chromosome 13 myeloma is a distinct entity with poor prognosis despite tandem autotransplants. Blood. 1998; 92:259A.

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. 1997; 24:229-237.

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

 

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