Cyclin D1 gene amplification in multiple myeloma and its impact on the disease outcome and drug resistance

Background: Cyclin D1 is involved in the normal regulation of the cell cycle and in neoplasia. Inhibition of cyclin D1 function markedly attenuates the proliferation of fibroblasts of colon, esophageal, lung, and pancreatic cancer. However, the prognostic value of overexpression of the cyclin D1 gene in multiple myeloma (MM) is still a point of debate. This study aims at evaluating the prognostic significance of cyclin D1 gene amplification in MM and whether it is correlated with MDR1 expression as an indicator of chemoresistance.Patients and methods: Twenty-five patients with MM were studied retrospectively. Cyclin D1 gene amplification was studied in bone marrow biopsies of these patients by fluorescence in-situ hybridization. Immunohistochemical study of the bone marrow biopsies was carried out to detect multidrug resistance (MDR1) gene expression. The correlations between the cyclin D1 gene amplification on the one hand and overall survival and MDR1 expression on the other were studied and analyzed statistically.Results: Cyclin D1 gene amplification was found in 20% of patients with myeloma and was associated with a higher percentage of plasma cell infiltration of the bone marrow and increase liability for multiple osteolytic lesions. Cyclin D1-positive patients had a significantly lower progression-free and overall survival and higher levels of MDR1 compared with cyclin D1-negative patients. Cyclin D1 levels showed a statistically highly significant positive correlation with MDR1 levels (r: 0.802 and P 0.0001).Conclusion: We suggest that there is an association between cyclin D1 gene amplification and higher disease severity, unfavorable prognosis, and increased expression of MDR1 in patients with MM.