engleski

Transcription factors of the zinc finger family in human disorders

Development of the lymphoid system is dependent on the activity of a transcription factor family encoded by Ikaros, Aiolos and Helios genes. These transcription factors are alternative splicing variants of primary RNA transcripts and they belong to the family of zinc finger proteins that specifically bind to DNA. It has been shown in mice that dimerization deficient isoforms of at least one of these transcription factors, the Ikaros gene, fail to transactivate target genes, and lead to lymphoproliferation and lymphoma development. On the other hand some authors found that Ikaros and related proteins can repress transcription from specific promotors in a cell type dependent manner. The aim of the present study is to analyse human lymphoid malignancies in order to check weather Ikaros, Aiolos or Helios expression in these disorders is impaired. By means of RT-nested-PCR method and specific primers for these genes we analysed their expression in human lymphoid cell lines (Jurkat, MOLT, NALM) and in lymph nodes from Hodgkin’s and Non-Hodgkin’s lymphoma patients. Our results show Ikaros expression in all tested samples. We found Aiolos being differentially expressed in adult human lymphoma. In 10 out of 18 lymphoma, Aiolos transcripts were detected. An additional smaller transcript was apparent in one of these lymphoma specimens. However even in the cases, where transcripts were detected, it is possible they are unfunctional splicing variants resulting from point mutations. Sequencing of the transcripts will give us more insight in the nature of transcripts and their relevance in lymphoproliferative disease development.

transcription factors; human malignancies; lymphocytes

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