engleski

Transcription factors in human malignancies

Development of the lymphoid system is dependent on the activity of a family of transcription factors encoded by the Ikaros and related genes. It has been shown that Ikaros transcription factors belong to the family of zinc finger proteins responsible for specific DNA binding. These transcription factors are alternate splicing products of primary RNA transcripts of the Ikaros gene. A mutation in the DNA binding domain introduced into mice (knock out mice Ikaros-/-) results in a complete block in lymphocyte development whereas other hemopoietic lineages develop normally. Heterozygous mice for the Ikaros mutation with the initially normal lymphocyte development, undergo changes accompanied by lymphoproliferation and development of leukaemia and lymphoma. It has been shown that the developing malignant clones have lost the single Ikaros wild type allele. Since the human homologue of the Ikaros gene has been cloned, we could analyze lymphocytes from several human lymphoid disorders to determine whether there is a change in the transcription factor genes expression in human malignant clones.

lymphoid system; transcription factors; leukaemia; lymphoma

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