Blood. Red cells & iron最新文献

{"title":"Multiomics signatures of hemolysis and vesiculation in stored red blood cells.","authors":"Monika Dzieciatkowska, Daniel Stephenson, Travis Nemkov, Erika G Marques de Menezes, Mars Stone, Gregory R Keele, Grier P Page, Steve Kleinman, Michael P Busch, Philip J Norris, Angelo D'Alessandro","doi":"10.1016/j.brci.2026.100142","DOIUrl":"https://doi.org/10.1016/j.brci.2026.100142","url":null,"abstract":"<p><p>Substantial donor-to-donor heterogeneity shapes red blood cell (RBC) storage biology, but the extent to which integrated donor and molecular measurements capture hemolysis and extracellular-vesicle (EV) phenotypes remains incompletely defined. We analyzed the tail-enriched REDS-III RBC-Omics recalled cohort using one storage-day-42 record from 649 donors. Demographic, complete blood count/ferritin, trace-element, metabolomic, lipidomic, and proteomic predictor blocks were benchmarked for three hemolysis and five EV outcomes. The molecular predictors and most outcomes were measured concurrently at day 42; change in total EVs was day 42 minus day 10. Ridge models used 10 repeats of five-fold outer cross-validation with five-fold inner tuning and fully fold-contained preprocessing and feature screening. Mean Pearson correlations were highest for osmotic hemolysis (r=0.63; full model), oxidative hemolysis (r=0.56; full model), RBC-derived CD235a+CD108- EVs (r=0.47; metabolomics), storage hemolysis (r=0.43; full model), and platelet-derived CD41a+CD62p- EVs (r=0.47; metabolomics). Change in total EVs and RBC-derived CD235a+CD108+ EVs were more modest (r=0.27 and 0.26, respectively), whereas total EV counts were not predicted above chance. Max-block permutation testing supported signal for seven outcomes (Benjamini-Hochberg q=0.006) but not total EVs (q=0.726). Elastic-net sensitivity analysis reproduced the principal ranking. Thus, day-42 storage phenotypes contain endpoint-specific distributed molecular signatures. These internally validated, cross-sectional results from a phenotype-enriched cohort do not establish prospective forecasting or transportability to routine donor populations; external validation is required.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-6-Phosphate Dehydrogenase Deficiency Reprograms Macrophage Metabolism in Hyperlipidemia.","authors":"Christopher M Clements, Megan Mazzei, Sydney Blimbaum, Ariel M Hay, Francesca I Cendali, Monika Dzieciatkowska, Sotirios P Fortis, Julie A Reisz, Brett P Ransegnola, Coleen A McNamara, James C Zimring, Angelo D'Alessandro","doi":"10.1016/j.brci.2026.100119","DOIUrl":"10.1016/j.brci.2026.100119","url":null,"abstract":"<p><p>Macrophages regulate inflammatory responses in hyperlipidemia and dysmetabolic states while performing a critical homeostatic function by clearing damaged or senescent red blood cells (RBCs) through erythrophagocytosis. This process delivers heme and iron that must be detoxified and recycled through NADPH-dependent pathways. Glucose-6-phosphate dehydrogenase deficiency (G6PDd), affecting ~6% of the global population, limits NADPH generation and predisposes RBCs to oxidative damage and hemolysis. Whether G6PD deficiency alters macrophage metabolic responses to RBC clearance in hyperlipidemic environments remains unknown. Humanized mouse models expressing canonical (hG6PD_ND), African (hG6PD_A-), or Mediterranean (hG6PD_Med-) G6PD variants were exposed to Western diet-induced hyperlipidemia. RBCs, plasma, and splenic macrophages were analyzed using metabolomics, lipidomics/oxylipin profiling, and quantitative proteomics. Hyperlipidemia increased circulating lipid species and altered RBC metabolism, while G6PD deficiency selectively reduced pentose phosphate pathway intermediates. Plasma metabolomics revealed signatures consistent with increased hemolysis in hyperlipidemic G6PD-deficient mice. Splenic macrophages from G6PDd animals showed biochemical evidence of erythrophagocytosis, glutathione depletion, and remodeling of central carbon metabolism. Variant-specific alterations included increased glycolytic flux, disrupted TCA cycle activity, and elevated succinate/fumarate ratios consistent with mitochondrial dysfunction. Proteomics revealed extensive mitochondrial and proteasomal remodeling. G6PD deficiency and hyperlipidemia converge to reprogram macrophage metabolism through NADPH limitation, redox imbalance, and impaired handling of RBC-derived metabolites. These findings identify an NADPH-dependent metabolic vulnerability linking RBC fragility, erythrophagocytosis, and inflammatory macrophage reprogramming.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red blood cell metabolome maps disease burden, mutation class, and splenectomy status in hereditary spherocytosis.","authors":"Travis Nemkov, Philippe Connes, Elie Nader, Romain Carin, Manon Casabianca, Alexandra Gauthier, Marie Martin, Camille Boisson, Céline Renoux, Nathalie Granier, Arnaud Hot, Solene Poutrel, Giovanna Cannas, Yves Bertrand, Philippe Joly, Angelo D'Alessandro","doi":"10.1016/j.brci.2026.100133","DOIUrl":"10.1016/j.brci.2026.100133","url":null,"abstract":"<p><p>Hereditary spherocytosis (HS) is caused by inherited defects in red blood cell (RBC) membrane and membrane-skeletal proteins, but the metabolic features associated with genotype, splenic selection, RBC injury, and clinical burden remain incompletely resolved. We performed RBC metabolomics in the VASCUSPHERO cohort, including 16 controls and 22 HS samples, and integrated omics data with splenectomy status, RBC deformability, microparticles, phosphatidylserine exposure, reactive oxygen species, calcium, CD47, complete blood count traits, and leukocyte subsets. The HS cohort included 12 spectrin beta, erythrocytic (SPTB)-only cases, 5 solute carrier family 4 member 1 (SLC4A1)/band 3 cases, 4 ankyrin 1 (ANK1)-only cases, and 1 combined ANK1/SPTB case. HS and control samples differed in global metabolomic space, with changes involving acylcarnitines, polyamines, pantothenate metabolism, gamma-glutamyl metabolites, sulfur metabolism, bile acids, and glutathione-related pathways. Metabolite and pathway scores correlated with reticulocytosis, deformability, RBC injury markers, and hematologic traits. Mutation-stratified analyses identified genotype-associated structure, whereas a cross-sectional analysis within SPTB-mutant HS identified splenectomy-associated metabolic and phenotypic differences. An exploratory, phenotype-derived burden score prioritized pantothenate, N1-acetylspermidine, N1-acetylspermine, gamma-glutamylputrescine, and selected acylcarnitines as candidate metabolic reporters. These findings position the RBC metabolome as an integrated, but not yet clinically validated, readout of membrane genetics, hemolytic stress, and splenectomy-associated remodeling. The Vascusphero project is a registered trail in ClinicalTrials.gov with identifier: NCT04451785 (https://clinicaltrials.gov/study/NCT04451785).</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium-associated BHMT2 and DMGDH loci connect one-carbon metabolism, selenoprotein biology, and red blood cell fragility.","authors":"Daniel Stephenson, Gregory R Keele, Julie A Reisz, Travis Nemkov, Amy Argabright, Mars Stone, Steve Kleinman, Michael P Busch, Philip J Norris, Grier P Page, Angelo D'Alessandro","doi":"10.1016/j.brci.2026.100132","DOIUrl":"10.1016/j.brci.2026.100132","url":null,"abstract":"<p><p>Storage of red blood cells (RBCs) in the blood bank promotes the accumulation of lesions, including metabolic decline, oxidative injury, membrane remodeling, vesiculation, and hemolysis. Genetic and multi-omic studies implicate iron-dependent lipid peroxidation and ferroptosis-like biology in poor RBC storage quality and post-transfusion recovery, highlighting GPX4, a selenium-dependent antioxidant enzyme, as a candidate modifier of stored RBC fragility. Although the genetic and omic determinants of GPX4 heterogeneity in donated RBCs have been explored, inter-donor variability in RBC selenium levels remains untested. To bridge this gap, selenium was measured by inductively coupled plasma mass spectrometry in 637 blood donors and integrated with stored RBC metabolomics, lipidomics, proteomics, extracellular vesicle and mitochondrial DNA markers, hemolysis phenotypes, and genotypes. Selenium showed broad inter-donor variation but minimal association with age, sex, or BMI. Selenium correlated with day-42 RBC multi-omic features, including iron, zinc, metabolites, lipids, proteins, and EV/mtDNA markers, and showed modest associations with osmotic hemolysis and complete blood count hemoglobin levels. Comparison of high- versus low-selenium donors identified differences in selected selenoprotein trajectories, strongest for GPX1. GWAS of selenium identified chromosome 5 loci near BHMT2 and DMGDH, including an intronic BHMT2-region variant and a DMGDH S279P missense variant. In approximately 13,000 donors from the REDS RBC-Omics index cohort, these loci associated with one-carbon metabolites, selenium-related proteins, detectable RBC selenoproteins, and osmotic hemolysis. These data identify selenium as a genetically anchored axis of RBC storage biology linking one-carbon metabolism, selenoprotein/redox pathways, and selected features of erythrocyte fragility.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain MRI and cognitive outcomes in adults with sickle cell disease treated with crizanlizumab.","authors":"Yan Wang, Slim Fellah, Kristina Rankine, Martin N Reis, Serguei Astafiev, Lauren Brewer, Morey Blinder, Allison A King, Yasheng Chen, Sheng-Kwei Song, Hongyu An, Andria L Ford","doi":"10.1016/j.brci.2026.100099","DOIUrl":"10.1016/j.brci.2026.100099","url":null,"abstract":"","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":"100099"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of erythroblastic island and tissue macrophages using a novel CD169-tdTomato-Cre mouse model and scRNA-seq.","authors":"Donghao Liu, Huan Zhang, Qianqian Yang, Anqi Guo, Huizhi Zhao, Xinhua Guo, Karina Yazdanbakhsh, Xiuli An","doi":"10.1016/j.brci.2026.100100","DOIUrl":"10.1016/j.brci.2026.100100","url":null,"abstract":"<p><p>Macrophages play diverse roles, including supporting erythropoiesis. CD169 is a specific marker for macrophages. However, recent studies showed that anti-CD169 staining detected nonmacrophages, raising the concern for using anti-CD169 antibody to correctly assign macrophages. Genetically engineered mouse models provide another means of monitoring gene expression. However, no mouse model is currently available to directly monitor CD169 expression. Erythropoiesis relies on macrophage-mediated iron recycling for iron supply. Although it is established that spleen (SP) macrophages play critical roles in erythrophagocytosis and iron recycling, whether and how other tissue macrophages are involved remain incompletely understood. To address these issues, we generated CD169-tdTomato-Cre mice. We also compared various tissue macrophages by single-cell RNA sequencing, flow cytometry, and cytospin analyses. We showed that CD169-tdTomato was detected and that CD169-Cre-mediated recombination occurred only in macrophages. Notably, bone marrow (BM) F4/80⁺CD169⁺ macrophages resemble erythroblastic island macrophages, as demonstrated by the expression of Epor along with other macrophage feature genes. A comparison of tissue macrophages revealed significant differences, including erythrophagocytosis by SP and BM macrophages, but not liver macrophages, at steady state; differential expression of the macrophage surface markers CD169, Vcam1, Cx3cr1, and Csf1r and the iron recycling genes Hmox1, Spic, and CD91; and selective expression of globin genes in lung macrophages. Our findings have uncovered previously unknown differences among tissue macrophages and provide novel insights into the mechanisms by which tissue macrophages participate in iron recycling to support erythropoiesis. The novel dual-functional CD169-tdTomato-Cre mouse line will have broad applications for studies of gene function in macrophages and their role in modulating erythropoiesis.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":"100100"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"With or Without You: Do Human EBIs Need a Central Macrophage?","authors":"Lionel Blanc","doi":"10.1016/j.brci.2026.100107","DOIUrl":"10.1016/j.brci.2026.100107","url":null,"abstract":"","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148915131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically based ferritin thresholds for defining iron deficiency in U.S. Children 5-14 years.","authors":"Yaw Addo, Maria Elena D Jefferds, Mica Jenkins, Gary M Brittenham, Zuguo Mei","doi":"10.1016/j.brci.2026.100093","DOIUrl":"https://doi.org/10.1016/j.brci.2026.100093","url":null,"abstract":"<p><strong>Background and objective: </strong>Iron deficiency (ID) is the most predominant nutritional deficiency globally. The current CDC iron guideline for ID screening uses serum ferritin (Ft) ≤15 μg/L for all individuals 6 months and older and was based on bone-marrow assessment. We aimed to evaluate physiologically based Ft thresholds for defining ID in children aged 5-14 years.</p><p><strong>Methods: </strong>Ferritin and hemoglobin (Hb) data were analyzed from 3765 apparently healthy (no inflammation, infection, or risk of iron overload) US children, since such data are an indicator of iron-deficient erythropoiesis, erythrocyte zinc protoporphyrin (eZnPP). Nonlinear ferritin concentration curves (Hb-Ft, eZnPP-Ft) and differential equations were applied to identify ferritin thresholds at ID onset with inflection minima and plateau for each iron analyte.</p><p><strong>Results: </strong>Mean age was 10.3 years. The ferritin curve inflection for ID occurred at 23.9 μg/L (95% confidence interval, 21.7-27.3) with Hb and 25.0 μg/L (23.8-27.1) with eZnPP. No inter-analyte (<i>P</i> = 0.67), age (<i>P</i> = 0.49 with Hb, <i>P</i> = 0.95 with eZnPP), or sex (<i>P</i> = 0.39) differences observed. ID prevalence was 9.0% (7.3-10.7), and ID anemia (IDA) 0.5% (0.3-0.8) using CDC thresholds, versus 30.0% (27.4-32.5) and IDA was 1.0% (0.6-1.3)% using physiologically based thresholds.</p><p><strong>Conclusion: </strong>Physiologically based ferritin thresholds for ID onset were consistently higher than current CDC thresholds across iron analyte, age, and sex. IDA remained unchanged with physiologically based thresholds, suggesting that anemia is not an adequate proxy for ID screening, and clinicians should consider higher ferritin as a functional threshold for defining ID in children.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13693696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle red blood cell/Siglec-9 interactions contribute to neutrophil activation in SCD and are associated with survival.","authors":"Grace M Lee, Kimberly Boyle, Milena Batchvarova, Martha Delahunty, Marilyn J Telen","doi":"10.1016/j.brci.2026.100074","DOIUrl":"10.1016/j.brci.2026.100074","url":null,"abstract":"<p><p>Sialic acid-binding Ig-like lectin-9 (Siglec-9) is a neutrophil inhibitory receptor. Prior studies have shown that sickle red blood cells (SS RBCs) abnormally engage neutrophil Siglec-9, suggesting that SS RBCs may not be able to effectively inhibit neutrophil activation. We examined SS RBC/Siglec-9 interactions and determined the effect of SS RBCs on Siglec-9 expression and neutrophil function. Using a novel monoclonal antibody-specific immobilization of erythrocyte antigen (MAIEA) assay, we demonstrated that SS RBCs have significantly decreased glycophorin A (GPA) and glycophorin B (GPB)-mediated binding to Siglec-9. Furthermore, exposure of healthy neutrophils to SS RBCs but not healthy AA RBCs induced shedding of Siglec-9 from neutrophil surfaces <i>in vitro</i>. <i>Ex vivo</i>, sickle cell disease (SCD) patients had fewer Siglec-9 positive neutrophils and elevated plasma soluble Siglec-9. Disruption of SS RBC/Siglec-9 interactions, both by desialylating RBCs and by blocking neutrophil Siglec-9, enhanced SS RBC-induced but not healthy AA RBC-induced neutrophil extracellular trap (NET) release. Finally, in a cohort of 32 SCD patients, soluble Siglec-9 was correlated with fetal hemoglobin (HbF), soluble intercellular adhesion molecule-1 (sICAM-1), and overall mortality. These studies demonstrate that unlike AA RBCs, SS RBCs not only directly activate neutrophils, but they also induce loss of neutrophil Siglec-9 and abnormally engage residual Siglec-9. Our findings suggest that neutrophil activation in SCD is a result of both direct activation and ineffective inhibition of neutrophils by SS RBCs.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-26a delivery increases erythroid expansion in models of Diamond-Blackfan anemia.","authors":"Jaqueline Mercado, Mallika Saxena, Gavin M Traber, Ryan S Sathianathen, Bertil Glader, Paraic Kenny, Kathleen M Sakamoto, Mark C Wilkes","doi":"10.1016/j.brci.2026.100104","DOIUrl":"https://doi.org/10.1016/j.brci.2026.100104","url":null,"abstract":"<p><p>Diamond-Blackfan anemia (DBA) is a pure red blood cell aplasia with a predisposition toward cancer. In DBA erythroid progenitors, nemo-like kinase (NLK) is activated, and mammalian target of rapamycin complex 1 (mTORC1) activity is suppressed. Systemic leucine administration high enough to hyperstimulate mTORC1 improves erythroid expansion in patients and animal models of DBA. However, leucine at such high doses significantly increases malignant transformation of nonerythroid cells upon exposure to carcinogens, heightening cancer risk in these patients. Here we show that exosomal delivery of miR-26a restores basal mTORC1 activity in erythroid progenitors by targeting the NLK transcript for degradation. miR-26a delivery does not hyperstimulate mTORC1, but removal of NLK-mediated mTORC1 suppression primes erythroid cells for mTORC1 hyperstimulation at a 10-fold lower systemic dose of leucine. Delivery of exosomal miR-26a supports optimal mTORC1 hyperstimulation and erythroid expansion with the administration of a leucine dose that does not increase the risk of transformation in nonerythroid cells, thus offering a safe, novel, and effective treatment strategy for increasing erythropoiesis in DBA.</p>","PeriodicalId":521056,"journal":{"name":"Blood. Red cells & iron","volume":"2 3","pages":"100104"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}