The aim of this study was to evaluate the effect of
everolimus, a
mammalian target of rapamycin (mTOR) inhibitor, on red blood cell parameters in the context of
iron homeostasis in patients with
tuberous sclerosis complex (
TSC) and evaluate its effect on cell size in vitro.
Everolimus has a significant impact on red blood cell parameters in patients with
TSC. The most common alteration was microcytosis. The mean MCV value decreased by 9.2%, 12%, and 11.8% after 3, 6, and 12 months of
everolimus treatment. The
iron level declined during the first 3 months, and human soluble
transferrin receptor concentration increased during 6 months of
therapy. The size of K562 cells decreased when cultured in the presence of 5 μM
everolimus by approximately 8%. The addition of
hemin to the cell culture with 5 μM
everolimus did not prevent any decrease in cell size. The stage of erythroid maturation did not affect the response to
everolimus. Our results showed that the mTOR inhibitor
everolimus caused red blood cell microcytosis in vivo and in vitro. This effect is not clearly related to a deficit of
iron and erythroid maturation. This observation confirms that mTOR signaling plays a complex role in the control of cell size.