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HR-MDS: High-risk myelodysplastic syndromes HSCs: Hematopoietic stem cells HSPCs: Hematopoietic stem and progenitor cells ICT: Iron chelation therapy IDH1/IDH2: Isocitrate dehydrogenase 1/2 IL-1: Interleukin 1 beta IL-7/10: Interleukin-7/10 IOL: Iron overload IPSS-R: Revised international prognostic scoring system LEPR: Leptin receptor LR-MDS: Low-risk myelodysplastic syndromes MDS: Myelodysplastic syndromes Mfn2: Mitofusin MMP: Mitochondrial membrane potential MPO: Myeloperoxidase mROS: Mitochondrial ROS MSCs: Mesenchymal stromal cells Mt ETC: Mitochondrial electron transport chain MTCH2: Mitochondrial carrier homologue 2 mTOR: Mammalian target of rapamycin MYH11: Myosin heavy chain 11 NAC: N-acetylcysteine NAD + : Nicotinamide adenine dinucleotide NADPH: Nicotinamide adenine dinucleotide phosphate Nes: Nestin NFAT: Nuclear factor of activated T cells NF-B: Nuclear factor B NG2: Neural-glial antigen 2 NHD13: NUP98-HOXD13 NLRP3: NLR family pyrin domain containing 3 NO : Nitric oxide NOX: NADPH oxidase NOX1-5: NADPH oxidase 15 NOXA1: NADPH oxidase activator 1 NOXO1: NADPH oxidase organizer 1 Nrf2: Nuclear factor erythroid-2 related factor 2 O 2 : Oxygen O 2 : Superoxide anion radicals O 3 : Ozone

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2.3 Safety and Tolerability Assessments Safety was assessed for the safety analysis set, defined as all enrolled participants who received at least one dose of SL BUP during the runin period

Additionally, Amifostine must be administered in a narrow time window (1530 min) before each radiation dose because of its short half-life 16 , constraining its clinical use 17

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