engleski

Regulators of Lymphocyte Development from Stem Cells

Lymphocytes have a limited life span and therefore they have to be continuously replaced throughout life. They arise from bone marrow multipotent hematopoietic stem cells, differentiate into committed lymphocyte precursors and develop into immunocompetent lymphocytes. An essential role in the commitment of hematopoietic progenitors into the lymphoid lineages as well in the choice of effector functions at later stages of development is played by transcription factors from the Ikaros family. Their role has been addressed by gene targeting and gene inactivation studies which identified Ikaros and other family members like Aiolos and Helios as transcription factors required for the maturation of lymphocytes. It has been shown that mice homozygous for a deletion in these genes undergo dramatic changes in their lymphocyte population and also those ageing animals with the same mutation develop lymphoproliferative disorders. Also, a number of studies show that Ikaros genes in both mice and human malignancies might be deregulated. Therefore we addressed the question weather a combination of transcription factor changes may contribute to the development of human lymphoma. We took advantage of the method for RNA extraction from formalin fixed paraffin embedded lymph nodes from lymphoma patients in order to have consistent and well defined groups of patients. We amplified mRNA and by real time PCR we defined the expression of Ikaros family members. Hence, we were able to analyze Ikaros, Aiolos and Helios mRNA from archive tissue specimens from patients with Hodgkin's and non- Hodgkin's lymphoma and follicular hyperplasia. Their potential role in disease development will be discussed.

transcription factors; stem cells; lymphocyte development; leukemia

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