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Background: Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma (CTCL). Arsenic trioxide (As2O3) has recently been shown to be effective against leukemias, so we studied whether As2O3 induces apoptosis of CTCL cells in vitro. We further investigated if As2O3 is effective in a MF mouse model. Material and methods: Annexin V/7-amino-actinomycin-D stainings were carried out to investigate if As2O3 induced apoptosis of CTCL cell lines. To study the underlying mechanisms, the effects of As2O3 on various transcription factors and apoptosis regulating proteins were analyzed by western blots, electrophoretic mobility shift assays and transcription factor enzyme-linked immunosorbent assays. The ability of As2O3 to induce tumor regression was investigated in a MF mouse model. Results: As2O3-induced apoptosis was paralleled by a reduction of the DNA-binding activities of transcription factors of the NFkB and signal transducer and activator of transcription gene families and reduced expression of the antiapoptotic proteins bcl-1, bcl-xL and mcl-1. Local injections of 200 μM As2O3 into tumors caused complete remissions in five of six mice and one partial remission. Conclusions: As2O3 induced apoptosis of CTCL cells by the down-regulation of transcription factors that stimulate the expression of antiapoptotic genes. Local injection of As2O3 into MF tumor-bearing mice resulted in tumor regression

The finding in colon carcinoma that cancerogenesis is a sequence of activation of different oncogenes and inactivation of tumor suppressor genes has increased the efforts to identify the genes that areresponsible for the progression of different kinds of cancer. Many activated oncogenes and inactivated tumor suppressor genes have been detected in cancer cells during the last decades, but for most cancers no network or sequence of oncogenes could be identified that could explain the progression of the disease and allow a molecular staging of the disease. Several strategies have been tried to find the genes that make cancer cells different from their normal counterparts, however, mostly only with little success. In this review article it will be reported how the strategy of transcription factor profiling helped to identify the genes that are responsible for the progression of two kinds of cutaneous lymphomas: Mycosis fungoides and the Sézary syndrome. By this way we were able to identify several agents that may be the prototypes of new drugs to fight these diseases.