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Effects of rapamycin on accumulation of α ‐, β ‐ and γ ‐globin mRNAs in erythroid precursor cells from β ‐thalassaemia patients
Author(s) -
Fibach Eitan,
Bianchi Nicoletta,
Borgatti Monica,
Zuccato Cristina,
Finotti Alessia,
Lampronti Ilaria,
Prus Eugenia,
Mischiati Carlo,
Gambari Roberto
Publication year - 2006
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2006.00731.x
Subject(s) - globin , sirolimus , biology , messenger rna , progenitor cell , microbiology and biotechnology , hemoglobinopathy , cell culture , stem cell , gene , immunology , hemolytic anemia , biochemistry , genetics
We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 β ‐thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two‐phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the β ‐thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to γ ‐globin mRNA accumulation, being only minor for β ‐globin and none for α ‐globin mRNAs. The ability of rapamycin to preferentially increase γ ‐globin mRNA content and production of HbF in erythroid precursor cells from β ‐thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti‐rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in β ‐thalassaemia and sickle cell anaemia.