{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:43:28Z","timestamp":1790196208880,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Br. J. Biomed. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The \u03b2-thalassemias are inherited genetic disorders affecting the hematopoietic system and caused by mutations of the adult \u03b2-globin gene, leading to low or absent production of adult hemoglobin. In addition, an excess of free \u03b1-globin is associated with ineffective erythropoiesis. In fact, the free \u03b1-globin molecules are prone to precipitate, causing toxicity to the erythroid cells, and interference with red cell maturation. In order to counteract the detrimental effects of the excess of \u03b1-globin, two pathways might be activated in \u03b2-thalassemia erythroid cells, i.e. Unc-51-like kinase 1 (Ulk-1)-mediated induction of autophagy and increased expression of the \u03b1-hemoglobin stabilizing protein (AHSP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>The studied case was a male transfusion dependent TM (Thalassemia Major) patient, aged 43 years, with a \u03b2<jats:sup>0<\/jats:sup>39\/\u03b2<jats:sup>+<\/jats:sup>IVSI-110 genotype (XmnI polymorphism: -\/-), starting the first blood transfusion when he was 5 months old, and participating to the NCT03877809 (Sirthalaclin) clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of AHSP and Ulk-genes in Erythroid precursor cells (ErPCs) was studied by Reverse transcription (RT)-qPCR and Western blotting ErPCs were isolated from the propositus after 90 and 180 days of treatment with sirolimus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>This study demonstrates for the first time that increase in the production of \u03b3-globin2 mRNA and HbF in ErPCs from a patient with \u03b2-thalassemia treated with sirolimus might be associated with co-induction of Ulk-1 and AHSP genes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/bjbs.2025.14311","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T06:00:41Z","timestamp":1751004041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Co-Induction of ULK-1 and AHSP mRNAs in Erythroid Precursor Cells Isolated From a Sirolimus-Treated \u03b2-Thalassemia Patient: A Case Report 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