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Accumulation of γ‐globin mRNA and induction of erythroid differentiation after treatment of human leukaemic K562 cells with tallimustine
Author(s) -
Bianchi Nicoletta,
Chiarabelli Cristiano,
Borgatti Monica,
Mischiati Carlo,
Fibach Eitan,
Gambari Roberto
Publication year - 2001
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 - 10.1046/j.1365-2141.2001.02843.x
Subject(s) - k562 cells , globin , inducer , biology , cellular differentiation , microbiology and biotechnology , fetal hemoglobin , cell culture , in vitro , gene , fetus , biochemistry , genetics , pregnancy
Human leukaemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5‐azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and cisplatin analogues. Differentiation of K562 cells is associated with an increase of expression of embryo‐fetal globin genes, such as the ζ‐, ε‐ and γ‐globin genes. The K562 cell line has been proposed as a very useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation stimulating γ‐globin synthesis could be considered for possible use in the therapy of haematological diseases associated with a failure in the expression of normal β‐globin genes. We have analysed the effects of tallimustine and distamycin on cell growth and differentiation of K562 cells. The results demonstrated that tallimustine is a potent inducer, while distamycin is a weak inducer, of K562 cell erythroid differentiation. Erythroid differentiation was associated with an increase of accumulation of γ‐globin mRNA and of production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition, tallimustine‐mediated erythroid induction occurred in the presence of activation of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of γ‐globin gene expression are strongly sustained by the finding that this compound stimulates fetal haemoglobin production in human erythroid precursor cells from normal subjects.