Everolimus is a potent inducer of erythroid differentiation and gamma-globin gene expression in human erythroid cells.
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.
Zuccato
Cristina
C
GenTech-for-Thal, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
Bianchi
Nicoletta
N
Borgatti
Monica
M
Lampronti
Ilaria
I
Massei
Francesco
F
Favre
Claudio
C
Gambari
Roberto
R
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
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D005914:Globins; D000068338:Everolimus; D020123:Sirolimus