title: Erythroid differentiation ability of butyric acid analogues: identification of basal chemical structures of new inducers of foetal haemoglobin.
abstract: Several investigations have demonstrated a mild clinical status in patients with β-globin disorders and congenital high persistence of foetal haemoglobin. This can be mimicked by a pharmacological increase of foetal γ-globin genes expression and foetal haemoglobin production. Our goal was to apply a multistep assay including few screening methods (benzidine staining, RT-PCR and HPLC analyses) and erythroid cellular model systems (the K562 cell line and erythroid precursors collected from peripheral blood) to select erythroid differentiation agents with foetal haemoglobin inducing potential. With this methodology, we have identified a butyric acid derivative, namely the 4174 cyclopropanecarboxylic acid compound, able to induce erythroid differentiation without antiproliferative effect in K562 cells and increase of γ-globin gene expression in erythroid precursor cells. The results are relevant for pharmacological treatments of haemoglobinopathies, including β-thalassaemia and sickle cell anaemia.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.affiliation: Department of Sciences, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy. Electronic address: cristiano.chiarabelli@uniroma3.it.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiarabelli
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.affiliation: Department of Chemistry, Chiesi Pharmaceuticals S.p.A., via Palermo 26/A, 43122 Parma, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Amari
authors.affiliation: Department of Chemistry, Chiesi Pharmaceuticals S.p.A., via Palermo 26/A, 43122 Parma, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Delcanale
authors.affiliation: Dipartimento Intraziendale di Medicina Trasfusionale, Ospedale "Santa Maria della Misericordia", Viale Tre Martiri 140, 45100 Rovigo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiavilli
authors.affiliation: Department of Hematology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem 91120, Israel.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Prus
authors.affiliation: Department of Hematology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem 91120, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Fibach
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, via Fossato di Mortara 74, 44121 Ferrara, Italy; Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassemia, Biotechnology Center, via Fossato di Mortara 64/b, 44121 Ferrara, Italy. Electronic address: gam@unife.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D020148:Butyric Acid / Q000737:chemistry* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D010330:Patents as Topic; D017086:beta-Thalassemia / Q000235:genetics / Q000473:pathology; D055545:gamma-Globins / Q000235:genetics
chemical_list: D055545:gamma-Globins; D020148:Butyric Acid; D005319:Fetal Hemoglobin
keywords: Butyrate analogues; Erythroid differentiation; Foetal haemoglobin production; Real-time PCR; γ-globin mRNA induction