title: Everolimus is a potent inducer of erythroid differentiation and gamma-globin gene expression in human erythroid cells.
abstract: We studied the effects of everolimus on the erythroid differentiation of human leukaemic K562 cells and on the cultures of erythroid progenitors derived from the peripheral blood of beta-thalassaemia patients. A quantitative real-time reverse-transcription polymerase chain reaction assay was employed for the quantification of the accumulation of globin mRNAs. The results obtained demonstrate that everolimus is a potent inducer of the erythroid differentiation of K562 cells. Erythroid induction is associated with an increase in alpha- and gamma-globin mRNAs. In erythroid precursor cells from 4 beta-thalassaemia patients, everolimus stimulated a preferential increase (ranging from 1.8- to 7.2-fold) in gamma-globin mRNA. Only minor effects were observed on the expression of alpha-globin genes. These results, in our opinion, are of interest as this compound is already employed in clinical trials as an anti-rejection agent following kidney transplantation. These data suggest that everolimus warrants further evaluation as a potential therapeutic drug in the treatment of beta-thalassaemia.
authors.affiliation: GenTech-for-Thal, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Francesco
authors.initials: F
authors.lastname: Massei
authors.forename: Claudio
authors.initials: C
authors.lastname: Favre
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D041905:Erythroid Cells / Q000166:cytology; D000068338:Everolimus; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D020014:K562 Cells; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D005914:Globins; D000068338:Everolimus; D020123:Sirolimus