engleski

Ikaros expression in human lymphoproliferative disorders

Commitment of hematopoietic progenitors into the lymphoid lineage, as well as the choice of effector function at later stages of this differentiation pathway, are dependent upon the tightly controlled transcription activation and/or repression of gene expression. Genetic studies have shown Ikaros to be essential regulator of lymphocyte differentiation and homeostasis.This transcription factor is alternative splicing variant of primary RNA transcripts and it belongs to the family of zinc finger proteins that specifically bind to DNA. It has been shown in mice that dimerization deficient isoforms of Ikaros fail to transactivate target genes, and lead to lymphoproliferation and lymphoma development. On the other hand 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 whether Ikaros expression in these disorders is impaired. We analysed Ikaros gene expression in human lymphocytes by amplifiing mRNA transcripts for the Ikaros isoforms Ik1, Ik2, Ik3 and Ik4. By means of RT-PCR method and specific primers we analysed Ikaros expression in human lymphoid cell lines (Jurkat, MOLT, NALM), in lymph nodes from Non-Hodgkin's lymphoma patients and in peripheral blood lymphocytes from chronic lymphocytic B cell leukaemia patients. In spite of the multiple defects observed in the lymphoid compartment of the Ikaros mutant mice, we found Ikaros gene expression at the level of mRNA in all tested human leukaemic cell lines and lymphomas. Still, we cannot exclude the possibility that Ikaros function might be impaired by point mutation(s), or by different levels of isoforme expression. Sequencing of the transcripts will give us more insight into ther nature and their relevance in lymphoproliferative disease development.

Ikaros; transcription factors; lymphoproliferative disorders

nije evidentirano