engleski

Correlation between Ikaros gene family members mRNA levels and the occurence of human lymphoma

Kruppel-like zinc finger transcription factors of the Ikaros family, including Aiolos and Helios proteins, are known to play major roles in the development of T and B lymphocytes. Studies of knock-out mice have shown that the absence of any of these factors causes arrests at different stages of lymphocyte development, while heterozygotes rapidly develop T and B cell lymphoma. Different isoforms of these proteins arise by alternative splicing of primary RNA transcripts. There is evidence that shorter isoforms (missing their DNA-binding Zn finger domains) can act in a dominant negative manner, forming heterodimers with DNA-binding isoforms and therefore preventing their regulatory activity, since such dimers cannot efficiently bind DNA. We investigate the expression of Aiolos and Helios in different human hematopoietic malignancies and correlate it with the type of disease. Using RT-PCR for amplification of Aiolos and Helios specific cDNA fragments, we analyzed the expression of these transcription factors in different human cell lines as well as in leukemic cells from patients with Morbus Hodgkin's and patients with non-Hodgkin's lymphoma. We also optimized a method for RNA extraction from formalin-fixed paraffin-embedded lymph node samples, thus overcoming a problem of availability of fresh material. Our results show different expression pattern of Aiolos and Helios in various human hematopoietic malignancies compared to healthy donors. Although we could not clearly correlate the differences in the expression of these factors with the type of disease, certain changes were noticed, so further studies are necessary for diagnostic and therapeutic advances in the human lymphoid diseases.

transcription factors; human; lymphoma

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