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Rapamycin‐mediated induction of γ ‐globin mRNA accumulation in human erythroid cells
Author(s) -
Mischiati Carlo,
Sereni Alessia,
Lampronti Ilaria,
Bianchi Nicoletta,
Borgatti Monica,
Prus Eugenia,
Fibach Eitan,
Gambari Roberto
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05083.x
Subject(s) - k562 cells , globin , biology , cell culture , inducer , fetal hemoglobin , leukemia , cell growth , transplantation , messenger rna , cancer research , microbiology and biotechnology , fetus , gene , immunology , medicine , biochemistry , genetics , pregnancy
Summary The present study aimed to determine whether rapamycin could increase the expression of γ ‐globin genes in human erythroid cells. Rapamycin is a macrocyclic lactone that possesses immunosuppressive, antifungal and anti‐tumour properties. This molecule is approved as an immunosuppressive agent for preventing rejection in patients receiving organ transplantation. To verify the activity of rapamycin, we employed two experimental cell systems, the human leukaemia K562 cell line and the two‐phase liquid culture of human erythroid progenitors isolated from normal donors and patients with β ‐thalassaemia. The results suggested that rapamycin, when compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and γ ‐globin mRNA accumulation in human leukaemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of rapamycin, γ ‐globin mRNA accumulation and fetal haemoglobin (HbF) production increased to levels that were higher than those obtained using hydroxyurea. These effects were not associated with inhibition of cell growth. Furthermore, rapamycin was found to increase HbF content in erythroid precursor cells from four β ‐thalassaemia patients. These results could have practical relevance, because pharmacologically mediated regulation of the expression of human γ ‐globin genes, leading to increased HbF, is considered a potential therapeutic approach in haematological disorders, including β ‐thalassaemia and sickle cell anaemia.