Polymorphisms of the tumor necrosis factor-α gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma
Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-α (TNF-α) in vitro. We studied single nucleotide polymorphisms at positions −308 and −238 of the TNF-α gene promoter and measured the...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[15 September 2002]
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| In: |
Blood
Year: 2002, Volume: 100, Issue: 6, Pages: 2263-2265 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.V100.6.2263 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.V100.6.2263 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497120510343 
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| Author Notes: | Kai Neben, Joannis Mytilineos, Thomas M. Moehler, Astrid Preiss, Alwin Kraemer, Anthony D. Ho, Gerhard Opelz, and Hartmut Goldschmidt |
| Summary: | Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-α (TNF-α) in vitro. We studied single nucleotide polymorphisms at positions −308 and −238 of the TNF-α gene promoter and measured the corresponding TNF-α cytokine levels in 81 patients (pts) with refractory and relapsed multiple myeloma (MM) who were treated with Thal. In myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with higher pretreatment TNF-α levels in peripheral blood (P = .047). After Thal administration, this TNF-238A group had a prolonged 12-month progression-free and overall survival of 86% and 100% versus 44% and 84% (P = .003 andP = .07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-α gene can affect TNF-α production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as “high producers” of TNF-α. |
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| Item Description: | Gesehen am 10.12.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.V100.6.2263 |