Histone deacetylase inhibitor FK228 is a potent inducer of human fetal hemoglobin.
We investigated the induction of the human fetal globin gene using five potent histone deacetylase (HDAC) inhibitors: FK-228, HC-Toxin, Trichostatin, MS-275, and Apicidin, using in vitro assays and cultures of primary human erythroblasts. The results showed that FK228 is the most potent inducer of fetal hemoglobin and exhibits its effects in picomolar concentrations. FK228 should be considered as a potential therapeutic for induction of fetal hemoglobin in patients with beta chain hemoglobinopathies.
Cao
Hua
H
Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA. huacao@u.washington.edu
Stamatoyannopoulos
George
G
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004900:Erythroblasts / Q000201:enzymology*; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006453:Hemoglobinopathies / Q000188:drug therapy / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006801:Humans
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D005319:Fetal Hemoglobin; C087123:romidepsin