Gene expression profiling of multiple myeloma cell lines after treatment with 5-aza-2′deoxycytidine and Trichostatin A

913 Multiple myeloma is a B-cell neoplasm which ranks as the second most frequently occurring hematologic malignancy. Epigenetic silencing of cancer-related genes is an important mechanism in the pathogenesis of multiple myeloma. We therefore performed a genome wide analysis using cDNA microarray to detect global changes in gene expression in the multiple myeloma cell lines U266 and MM1 induced by the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (AzaC) and the histone deacetylase inhibitor trichostatin A (TSA). The increase of expression was defined as ≥ 2-fold change in expression compared to untreated cells. In the cell line U266 we found 83 genes out of 22283 probe sets with an increase in expression after AzaC treatment and 110 genes with an increase in expression in AzaC/TSA-treated cells compared to untreated cells. The expression of 46 genes was up-regulated in AzaC-treated MM1 cells and in 112 genes after treatment with the AzaC/TSA combination. Among these genes there are several putative tumor suppressor genes including PFN1 ( Profilin1 ), NME4 , ST14 , PYCARD , DLEU1 and p57 . The expression of 6 and 28 genes was found to be up-regulated in both cell lines after AzaC and AzaC/TSA treatment, respectively. Selected genes will now be analyzed for their expression and methylation pattern in bone marrow aspirates from multiple myeloma patients. In conclusion, our results demonstrate that AzaC and AzaC/TSA reactivate the expression of by epigenetic mechanisms silenced genes. Reactivation of these genes using DNA methyltransferase inhibitors and histone deacetylase inhibitors may play a role in the future treatment of multiple myeloma patients.