Genomic loss of putative tumor suppressor gene E2A is crucial for a rare Sézary syndrome
08.08.11
Category: Scientific News
Fundamentally new insights into genesis and development of Sézary syndrome and possibly other human lymphomas
Scientists in Germany have succeeded in providing fundamentally new insights into the genesis and development of Sézary syndrome, which is largely unexplained to date. The malignant Sézary syndrome origin is a CD4+ T-lymphocyte from peripheral blood. Epidermotropism by neoplastic CD+ lymphocytes with the formation of Pautrier's microabscesses is the hallmark sign of the disease. In contrast to most other skin lymphomas, patients with Sézary syndrome manifest not only skin contamination but also presence of degenerate T-cells in the peripheral blood and lymph nodes even at the onset of the disease.
German researchers investigated highly purified tumor cells from patients with Sézary syndrome using array comparative genomic hybridization technique for hitherto unknown genetic changes. In doing so they identified areas in the genotype of these tumor cells that have become lost in many of the patients examined. A detailed analysis of these areas showed that one of the most frequently affected genes codes for a transcription factor. Transcription factors have key functions in the regulation of cellular gene activity.
According to Chalid Assaf from the Charité Klinik für Dermatologie, Venerologie und Allergologie the partial loss of the gene for transcription factor E2A appears to play an essential role in this context because the gene is normally of great importance for natural lymphocyte development. In mice a loss of this gene leads to the genesis of aggressive T cell lymphomas. However, a gene loss in one of the various human lymphoma classes had so far remained elusive.
The researchers also identified several E2A-regulated genes and signal paths in tumor cells, the mere deregulation of each of which is sufficient to enable a tumor to develop. Stephan Mathas, a scientist at the Charité Klinik für Hämatologie und Onkologie emphasized that the loss of E2A in Sézary syndrome is of crucial importance for the aggressive behavior of tumor cells because it contributes to more rapid, uncontrolled growth of cells. Consequently, it was directly proven for the first time that E2A in humans has the function of a tumor suppressor.
German researchers hope that these findings will lead to the development of new, more effective treatment concepts for patients with Sézary syndrome.
The study was supported by the 7th EU Framework Programme, Deutsche Forschungsgemeinschaft, Berliner Krebsgesellschaft, and Max Planck Innovation Fonds.
German researchers investigated highly purified tumor cells from patients with Sézary syndrome using array comparative genomic hybridization technique for hitherto unknown genetic changes. In doing so they identified areas in the genotype of these tumor cells that have become lost in many of the patients examined. A detailed analysis of these areas showed that one of the most frequently affected genes codes for a transcription factor. Transcription factors have key functions in the regulation of cellular gene activity.
According to Chalid Assaf from the Charité Klinik für Dermatologie, Venerologie und Allergologie the partial loss of the gene for transcription factor E2A appears to play an essential role in this context because the gene is normally of great importance for natural lymphocyte development. In mice a loss of this gene leads to the genesis of aggressive T cell lymphomas. However, a gene loss in one of the various human lymphoma classes had so far remained elusive.
The researchers also identified several E2A-regulated genes and signal paths in tumor cells, the mere deregulation of each of which is sufficient to enable a tumor to develop. Stephan Mathas, a scientist at the Charité Klinik für Hämatologie und Onkologie emphasized that the loss of E2A in Sézary syndrome is of crucial importance for the aggressive behavior of tumor cells because it contributes to more rapid, uncontrolled growth of cells. Consequently, it was directly proven for the first time that E2A in humans has the function of a tumor suppressor.
German researchers hope that these findings will lead to the development of new, more effective treatment concepts for patients with Sézary syndrome.
The study was supported by the 7th EU Framework Programme, Deutsche Forschungsgemeinschaft, Berliner Krebsgesellschaft, and Max Planck Innovation Fonds.
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