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New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration.

Abstract
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.
AuthorsJustyna Jakubowska, Bartłomiej Pawlik, Krystyna Wyka, Małgorzata Stolarska, Katarzyna Kotulska, Sergiusz Jóźwiak, Wojciech Młynarski, Joanna Trelińska
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 13 (Jun 24 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34202704 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Protein Kinase Inhibitors
  • Everolimus
  • Iron
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
Topics
  • Adolescent
  • Biomarkers
  • Cell Differentiation (drug effects)
  • Cell Line
  • Cell Size (drug effects)
  • Child
  • Child, Preschool
  • Erythrocyte Indices
  • Erythrocytes (drug effects, metabolism, pathology)
  • Everolimus (administration & dosage, adverse effects, pharmacology)
  • Flow Cytometry
  • Humans
  • Iron (metabolism)
  • K562 Cells
  • Protein Kinase Inhibitors (administration & dosage, adverse effects, pharmacology)
  • TOR Serine-Threonine Kinases (antagonists & inhibitors)

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