Recognition of Myeloma by MAGE-A3 Specific Cytotoxic T Lymphocytes Induced by Treatment with Azacitidine and MGCD0103
| Autor: | Bart Barlogie, John D. Shaughnessy, Susann Szmania, Tarun K. Garg, Katie L. Stone, Amberly Moreno-Bost, Jumei Shi, Frits van Rhee, H G Prentice |
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| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Blood. 112:3674-3674 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v112.11.3674.3674 |
| Popis: | Demethylating agents and histone deacetylase inhibitors (HDACi) are epigenetic modulators that can induce re-expression of tumor suppressor and cell cycle proteins that have been silenced through aberrant hypermethylation associated with tumoral transformation. Azacitidine (Aza) is a cytosine analogue that primarily affects RNA during transcription. However, DNA is also a target for demethylation during replication thereby increasing gene re-expression. Treatment with HDACi, such as MGCD0103 (MGC), can synergize with demethylating agents to boost the epigenetic effects of either drug used alone. Our gene expression profiling data shows that the cancer-testis antigen MAGE-A3 is expressed in 31% of myeloma patients at diagnosis and the frequency of expression is increased at relapse to 49% (n=51 paired samples, p Figure 1. Treatment with 50nM Aza and/or sequential MGC at 500 nM induces de nono expression of MAGE-A3 protein in the myeloma a cell line transfectant LP1 A68. Figure 1. Treatment with 50nM Aza and/or sequential MGC at 500 nM induces de nono expression of MAGE-A3 protein in the myeloma a cell line transfectant LP1 A68. Figure 2. Lysis of LP-1 A68 Aza/MGC treated targets by MAGE-A3 specific CTL effective. Figure 2. Lysis of LP-1 A68 Aza/MGC treated targets by MAGE-A3 specific CTL effective. |
| Databáze: | OpenAIRE |
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