{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:49:07Z","timestamp":1766137747834,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ5\/02229"],"award-info":[{"award-number":["2015\/19\/B\/NZ5\/02229"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"],"award-info":[{"award-number":["503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03bcM everolimus by approximately 8%. The addition of hemin to the cell culture with 5 \u03bcM 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.<\/jats:p>","DOI":"10.3390\/ijms22136802","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:01:38Z","timestamp":1624532498000},"page":"6802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration"],"prefix":"10.3390","volume":"22","author":[{"given":"Justyna","family":"Jakubowska","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-1033","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyna","family":"Wyka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Stolarska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kotulska","sequence":"additional","affiliation":[{"name":"Department of Neurology & Epileptology and Pediatric Rehabilitation, The Children\u2019s Memorial Health Institute, ul. Dzieci Polskich 20, 00-999 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-6326","authenticated-orcid":false,"given":"Sergiusz","family":"J\u00f3\u017awiak","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Medical University of Warsaw, ul. Banacha 1A, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-4274","authenticated-orcid":false,"given":"Joanna","family":"Treli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-3-319-91442-8_8","article-title":"Everolimus","volume":"Volume 211","author":"Martens","year":"2018","journal-title":"Small Molecules in Oncology. 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