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The human leukemic K562 cell line has been proposed as a useful in vitro model to study the molecular mechanism(s) regulating the expression of the human embryonic and fetal globin genes, as well as to determine the therapeutic potential of new differentiation-inducing compounds. This cell line exhibits a low proportion of hemoglobin (Hb) synthesizing cells under standard cell growth conditions, but it is capable of undergoing erythroid differentiation when treated with a variety of compounds, such as hemin, cytosine arabinoside (ara-C), butyric acid, 5-azacytidine, chromomycin and mithramycin, tallimustine, cisplatin and cisplatin analogs. Following erythroid induction of K562 cells, Hb Portland ([zeta]^sub 2^[gamma]^sub 2^) and Hb Gower 1 ([zeta]^sub 2^[epsilon]^sub 2^) accumulate, due to increase in the expression of human [zeta]-, [epsilon]- and [gamma]-globin genes. K562 cells are suitable for identifying inducers of fetal hemoglobin (HbF). However, after a preliminary screening, the molecules able to induce erythroid differentiation of K562 cells should be tested in the 2-phases culture systems of human erythroid precursors from peripheral blood, to obtain more informative results on the effects of inducers on HbF production.
KEY WORDS: K562 cells - [beta]-thalassemia - Fetal hemoglobin - Ara-C - Cytosine arabinoside.
Increase of fetal hemoglobin (HbF) leads to a significant improvement of the clinical status of patients affected by these hematological disorders, including [beta]-thalassemia and sickle cell anemia.1-3 Therefore, several studies have been focused on the screening of various agents able to upregulate the expression of the human [gamma]-globin genes, such as hormones, cytotoxic drugs, hemopoietic cytokines and short fatty acids as molecules capable of augmenting HbF levels in humans.4-13
In this respect, the availability of a cellular model system for the rapid screening of potential HbF inclucers could be of great interest.10, 14, 15 Among cellular systems available for the screening of drugs able to induce erythroid differentiation and possibly involved in reactivation of HbF production, the human erythroleukemia K562 cell line has been largely exploited.
This cell line has been indeed proposed as a useful in vitro model to study the molecular mechanism(s) regulating the expression of embryonic and fetal human globin genes,16-20 as well as to determine the therapeutic potential of new differentiation-inducing compounds.21-28
The K562 cell line has been isolated and characterized by Lozzio and Lozzio 29 from a...