The DNA-binding drugs mithramycin and chromomycin are powerful inducers of erythroid differentiation of human K562 cells
Nicoletta Bianchi,
Fabio Osti, Cristina Rutigliano,
Federica Ginanni Corradini,
Elena Borsetti,
Marina Tomassetti,
Carlo Mischiati,
Giordana Feriotto,
Roberto Gambari,
Nicoletta Bianchi
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorCristina Rutigliano
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorFederica Ginanni Corradini
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorElena Borsetti
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorMarina Tomassetti
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorCarlo Mischiati
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorGiordana Feriotto
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorRoberto Gambari
Department of Biochemistry and Molecular Biology,
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorNicoletta Bianchi,
Fabio Osti, Cristina Rutigliano,
Federica Ginanni Corradini,
Elena Borsetti,
Marina Tomassetti,
Carlo Mischiati,
Giordana Feriotto,
Roberto Gambari,
Nicoletta Bianchi
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorCristina Rutigliano
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorFederica Ginanni Corradini
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorElena Borsetti
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorMarina Tomassetti
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorCarlo Mischiati
Department of Biochemistry and Molecular Biology,
Search for more papers by this authorGiordana Feriotto
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorRoberto Gambari
Department of Biochemistry and Molecular Biology,
Biotechnology Centre, University of Ferrara, Ferrara, Italy
Search for more papers by this authorProfessor Roberto Gambari, Department of Biochemistry and Molecular Biology, Via L. Borsari 46, 44100 Ferrara, Italy.
Abstract
The human leukaemic K562 cell line can be induced in vitro to undergo erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine and cytosine arabinoside. Differentiation of K562 cells is associated with an increased expression of embryo-fetal globin genes, such as the ζ, ε and γ globin genes. Therefore the K562 cell line has been proposed as a 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 which stimulate γ-globin synthesis could be considered for possible use in the experimental therapy of those haematological diseases associated with a failure in the expression of adult β-globin genes. In this paper we demonstrated that the G + C selective DNA-binding drugs chromomycin and mithramycin were powerful inducers of erythroid differentiation of K562 cells. Erythroid differentiation was associated with an increase in the accumulation of (a) Hb Gower 1 and Hb Portland and (b) γ-globin mRNA.
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