We studied the effects of rapamycin on cultures of erythroid progenitors derived 
from the peripheral blood of 10 beta-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 
beta-thalassaemia patients studied and an increase of their overall Hb 
content/cell. The inducing effect of rapamycin was restricted to gamma-globin 
mRNA accumulation, being only minor for beta-globin and none for alpha-globin 
mRNAs. The ability of rapamycin to preferentially increase gamma-globin mRNA 
content and production of HbF in erythroid precursor cells from 
beta-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 beta-thalassaemia and 
sickle cell anaemia.