PMID- 34202704
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20231107
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 13
DP  - 2021 Jun 24
TI  - New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration.
LID - 10.3390/ijms22136802 [doi]
LID - 6802
AB  - 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 muM everolimus by approximately 8%. The addition of hemin to the cell culture 
      with 5 muM 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.
FAU - Jakubowska, Justyna
AU  - Jakubowska J
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
FAU - Pawlik, Bartlomiej
AU  - Pawlik B
AUID- ORCID: 0000-0002-8803-1033
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
AD  - Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 
      Warsaw, Poland.
FAU - Wyka, Krystyna
AU  - Wyka K
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
FAU - Stolarska, Malgorzata
AU  - Stolarska M
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
FAU - Kotulska, Katarzyna
AU  - Kotulska K
AD  - Department of Neurology & Epileptology and Pediatric Rehabilitation, The 
      Children's Memorial Health Institute, ul. Dzieci Polskich 20, 00-999 Warsaw, 
      Poland.
FAU - Jozwiak, Sergiusz
AU  - Jozwiak S
AUID- ORCID: 0000-0003-3350-6326
AD  - Department of Child Neurology, Medical University of Warsaw, ul. Banacha 1A, 
      02-097 Warsaw, Poland.
FAU - Mlynarski, Wojciech
AU  - Mlynarski W
AUID- ORCID: 0000-0003-2714-5851
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
FAU - Trelinska, Joanna
AU  - Trelinska J
AUID- ORCID: 0000-0003-1484-4274
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      ul. Sporna 36/50, 91-738 Lodz, Poland.
LA  - eng
GR  - 2015/19/B/NZ5/02229/Narodowe Centrum Nauki/
GR  - 503/1-090-04/503-11-003/Uniwersytet Medyczny w Lodzi/
GR  - 503/1-090-04/503-11-001-19/Uniwersytet Medyczny w Lodzi/
PT  - Journal Article
DEP - 20210624
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adolescent
MH  - Biomarkers
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Size/*drug effects
MH  - Child
MH  - Child, Preschool
MH  - Erythrocyte Indices
MH  - Erythrocytes/*drug effects/metabolism/*pathology
MH  - Everolimus/administration & dosage/adverse effects/pharmacology
MH  - Flow Cytometry
MH  - Humans
MH  - Iron/metabolism
MH  - K562 Cells
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC8268656
OTO - NOTNLM
OT  - K562 cells
OT  - everolimus
OT  - mTOR inhibitor
OT  - microcytosis of the red blood cells
COIS- Authors have neither financial relationships nor other conflicts of interest 
      relevant to this article to disclose.
EDAT- 2021/07/03 06:00
MHDA- 2021/07/27 06:00
PMCR- 2021/06/24
CRDT- 2021/07/02 01:14
PHST- 2021/05/18 00:00 [received]
PHST- 2021/06/12 00:00 [revised]
PHST- 2021/06/22 00:00 [accepted]
PHST- 2021/07/02 01:14 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2021/06/24 00:00 [pmc-release]
AID - ijms22136802 [pii]
AID - ijms-22-06802 [pii]
AID - 10.3390/ijms22136802 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jun 24;22(13):6802. doi: 10.3390/ijms22136802.