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We first discussed the impact of the excess of free \u03b1-globin on the phenotype of \u03b2-thalassemia. We then reviewed studies focusing on the expression of \u03b1-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free \u03b1-globin on erythroid cells. Alternative processes controlling \u03b1-globin excess were also considered, including the activation of autophagy by \u03b2-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with \u03b2-thalassemia and other hemoglobinopathies for which reduction in \u03b1-globin excess is clinically beneficial.<\/jats:p>","DOI":"10.3390\/ijms25063400","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T05:14:07Z","timestamp":1710738847000},"page":"3400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Impact of \u03b1-Globin Gene Expression and \u03b1-Globin Modifiers on the Phenotype of \u03b2-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-5628","authenticated-orcid":false,"given":"Joanne","family":"Traeger-Synodinos","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia\u2019s Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Vrettou","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia\u2019s Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-4287","authenticated-orcid":false,"given":"Christalena","family":"Sofocleous","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, National and Kapodistrian University of Athens, St. Sophia\u2019s Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-3727","authenticated-orcid":false,"given":"Matteo","family":"Zurlo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, 40124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7638-515X","authenticated-orcid":false,"given":"Alessia","family":"Finotti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, 40124 Ferrara, Italy"},{"name":"Center \u201cChiara Gemmo and Elio Zago\u201d for the Research on Thalassemia, Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-6033","authenticated-orcid":false,"given":"Roberto","family":"Gambari","sequence":"additional","affiliation":[{"name":"Center \u201cChiara Gemmo and Elio Zago\u201d for the Research on Thalassemia, Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/35066048","article-title":"Phenotype-genotype relationships in monogenic disease: Lessons from the thalassaemias","volume":"2","author":"Weatherall","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0140-6736(11)60283-3","article-title":"Thalassaemia","volume":"379","author":"Higgs","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bcmd.2017.06.001","article-title":"Molecular basis of \u03b2 thalassemia and potential therapeutic targets","volume":"70","author":"Thein","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/03630269.2014.985831","article-title":"\u03b2-globin genes: Mutation hot-spots in the global thalassemia belt","volume":"39","author":"Kumar","year":"2015","journal-title":"Hemoglobin"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148022","DOI":"10.1016\/j.gene.2023.148022","article-title":"Global distribution of \u03b2-thalassemia mutations: An update","volume":"896","author":"Rao","year":"2023","journal-title":"Gene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/hmg\/10.4.339","article-title":"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16","volume":"10","author":"Daniels","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00438-022-01968-1","article-title":"Investigation of the mechanism of copy number variations involving the \u03b1-globin gene cluster on chromosome 16: Two case reports and literature review","volume":"298","author":"Zhu","year":"2023","journal-title":"Mol. Genet. Genom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1196\/annals.1345.012","article-title":"Understanding alpha-globin gene regulation: Aiming to improve the management of thalassemia","volume":"1054","author":"Higgs","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1750-1172-5-13","article-title":"Alpha-thalassaemia","volume":"5","author":"Harteveld","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.hoc.2010.08.005","article-title":"The molecular basis of \u03b1-thalassemia: A model for understanding human molecular genetics","volume":"24","author":"Higgs","year":"2010","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1365-2141.1982.tb03916.x","article-title":"The interaction of alpha thalassaemia with heterozygous beta thalassaemia","volume":"52","author":"Kanavakis","year":"1982","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0268-960X(87)90029-4","article-title":"Thalassaemia Intermedia","volume":"1","author":"Wainscoat","year":"1987","journal-title":"Blood Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bcmd.2003.12.005","article-title":"A rare example that coinheritance of a severe form of beta-thalassemia and alpha-thalassemia interact in a \u2018\u2018synergistic\u2019\u2019 manner to balance the phenotype of classic thalassemic syndromes","volume":"32","author":"Kanavakis","year":"2004","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1365-2141.1978.tb01109.x","article-title":"A unique thalassaemic syndrome: Homozygous alpha-thalassaemia + homozygous beta-thalassaemia","volume":"39","author":"Loukopoulos","year":"1978","journal-title":"Br. J. Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3109\/03630269.2015.1047513","article-title":"Elevated Hb A\u2082 Levels in a Patient with a Compound Heterozygosity for the (\u03b2\u207a)-31 (A > G) and (\u03b2\u2070) Codon 17 (A > T) Mutations Together with a Single \u03b1-Globin Gene","volume":"39","author":"Panyasai","year":"2015","journal-title":"Hemoglobin"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1046\/j.1365-2141.1996.d01-1939.x","article-title":"The triplicated alpha-globin gene locus in beta-thalassaemia heterozygotes: Clinical, haematological, biosynthetic and molecular studies","volume":"95","author":"Kanavakis","year":"1996","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/(SICI)1096-8652(199706)55:2<83::AID-AJH6>3.0.CO;2-Z","article-title":"Different hematological phenotypes caused by the interaction of triplicated alpha-globin genes and heterozygous beta-thalassemia","volume":"55","author":"Camaschella","year":"1997","journal-title":"Am. J. Hematol."},{"key":"ref_18","first-page":"171","article-title":"Clinical phenotype of triplicated alpha-globin genes and heterozygosity for beta0-thalassemia in Chinese subjects","volume":"8","author":"Ma","year":"2001","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e762","DOI":"10.1097\/MPH.0000000000001730","article-title":"Coinheritance of Triplicated Alpha-Globin Gene and Beta-Thalassemia Mutations in Adulthood: Ten Years of Referrals in Northern Greece","volume":"42","author":"Theodoridou","year":"2020","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/ejh.13923","article-title":"Hematological and genetic profiles of persons with co-inherited heterozygous \u03b2-thalassemia and supernumerary \u03b1-globin genes","volume":"110","author":"Sundaresan","year":"2023","journal-title":"Eur. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"866396","DOI":"10.3389\/fmed.2022.866396","article-title":"\u03b2-Thalassemia Intermedia: Interaction of \u03b1-Globin Gene Triplication With \u03b2-thalassemia Heterozygous in Spain","volume":"9","author":"Ropero","year":"2022","journal-title":"Front. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e494","DOI":"10.1097\/MPH.0000000000001470","article-title":"Non-transfusion-dependent \u03b2-Thalassemia Because of a Single \u03b2-Thalassemia Mutation and Coinherited \u03b1-Globin Gene Triplication: Need for Increased Awareness to Prevent Incorrect and Delayed Diagnosis","volume":"42","author":"Gurunathan","year":"2020","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/03630260902827684","article-title":"Frequency of alpha-globin gene triplications and their interaction with betathalassemia mutations","volume":"33","author":"Giordano","year":"2009","journal-title":"Hemoglobin"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/jha2.262","article-title":"Alpha-globin gene triplication and its effect in beta-thalassemia carrier, sickle cell trait, and healthy individual","volume":"2","author":"Hamid","year":"2021","journal-title":"EJHaem"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1007\/BF01649440","article-title":"Interaction of heterozygous beta (0)-thalassemia and triplicated alpha globin loci in a Swiss-Spanish family","volume":"69","author":"Beris","year":"1991","journal-title":"Klin. Wochenschr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1046\/j.1365-2141.1999.01451.x","article-title":"Severe inclusion body beta-thalassaemia with haemolysis in a patient double heterozygous for beta(0)-thalassaemia and quadruplicated alpha-globin gene arrangement of the anti-4.2 type","volume":"105","author":"Beris","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1182\/blood.V62.5.1035.1035","article-title":"A Family with Segregating Triplicated Alpha Globin Loci and Beta Thalassemia","volume":"62","author":"Galanello","year":"1983","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1365-2141.1994.tb04743.x","article-title":"Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia","volume":"86","author":"Oron","year":"1994","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1365-2141.1984.tb03960.x","article-title":"Thalassaemia intermedia: A new molecular basis","volume":"56","author":"Thein","year":"1984","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bcmd.2007.11.006","article-title":"Segmental duplications involving the alpha-globin gene cluster are causing beta-thalassemia intermedia phenotypes in beta-thalassemia heterozygous patients","volume":"40","author":"Harteveld","year":"2008","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-2141.1987.tb01306.x","article-title":"Two different quadruplicated alpha globin gene arrangements","volume":"66","author":"Gu","year":"1987","journal-title":"Br. J. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1586\/17474086.2015.1075385","article-title":"Copy number variations of six and seven \u03b1-globin genes in a family with intermedia and major thalassemia phenotypes","volume":"8","author":"Farashi","year":"2015","journal-title":"Expert Rev. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/nyas.12988","article-title":"Understanding alpha-globin gene regulation and implications for the treatment of beta-thalassemia","volume":"1368","author":"Mettananda","year":"2016","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00438-022-01978-z","article-title":"CRISPR\/Cas9, a promising approach for the treatment of \u03b2-thalassemia: A systematic review","volume":"298","author":"Khiabani","year":"2023","journal-title":"Mol. Genet. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"901605","DOI":"10.3389\/fped.2022.901605","article-title":"Genetic Manipulation Strategies for \u03b2-Thalassemia: A Review","volume":"10","author":"Zakaria","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rahimmanesh, I., Boshtam, M., Kouhpayeh, S., Khanahmad, H., Dabiri, A., Ahangarzadeh, S., Esmaeili, Y., Bidram, E., Vaseghi, G., and Haghjooy Javanmard, S. (2022). Gene Editing-Based Technologies for Beta-hemoglobinopathies Treatment. Biology, 11.","DOI":"10.3390\/biology11060862"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"618111","DOI":"10.3389\/fgeed.2021.618111","article-title":"Recent Approaches for Manipulating Globin Gene Expression in Treating Hemoglobinopathies","volume":"3","author":"Mussolino","year":"2021","journal-title":"Front. Genome Ed."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Koniali, L., Lederer, C.W., and Kleanthous, M. (2021). Therapy Development by Genome Editing of Hematopoietic Stem Cells. Cells, 10.","DOI":"10.3390\/cells10061492"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40246-021-00329-0","article-title":"Genome-based therapeutic interventions for \u03b2-type hemoglobinopathies","volume":"15","author":"Karamperis","year":"2021","journal-title":"Hum. Genom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1204536","DOI":"10.3389\/fgeed.2023.1204536","article-title":"Combined approaches for increasing fetal hemoglobin (HbF) and de novo production of adult hemoglobin (HbA) in erythroid cells from \u03b2-thalassemia patients: Treatment with HbF inducers and CRISPR-Cas9 based genome editing","volume":"5","author":"Finotti","year":"2023","journal-title":"Front. Genome Ed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.hoc.2022.12.012","article-title":"Gene Therapy and Gene Editing for \u03b2-Thalassemia","volume":"37","author":"Christakopoulos","year":"2023","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Paschoudi, K., Yannaki, E., and Psatha, N. (2023). Precision Editing as a Therapeutic Approach for \u03b2-Hemoglobinopathies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119527"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1186\/s13287-020-01876-4","article-title":"CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation","volume":"11","author":"Gabr","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3324\/haematol.2020.278238","article-title":"Correction of RNA splicing defect in \u03b2654-thalassemia mice using CRISPR\/Cas9 gene-editing technology","volume":"107","author":"Lu","year":"2022","journal-title":"Haematologica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.omtm.2021.03.025","article-title":"Efficient CRISPR-Cas9-based genome editing of \u03b2-globin gene on erythroid cells from homozygous \u03b2039-thalassemia patients","volume":"21","author":"Cosenza","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"752278","DOI":"10.3389\/fgeed.2021.752278","article-title":"Genetic and Epigenetic Therapies for \u03b2-Thalassaemia by Altering the Expression of \u03b1-Globin Gene","volume":"3","author":"Mettananda","year":"2021","journal-title":"Front. Genome Ed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/s41591-021-01284-y","article-title":"Gene replacement of \u03b1-globin with \u03b2-globin restores hemoglobin balance in \u03b2-thalassemia-derived hematopoietic stem and progenitor cells","volume":"27","author":"Cromer","year":"2021","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1182\/bloodadvances.2020001996","article-title":"Correction of \u03b2-thalassemia by CRISPR\/Cas9 editing of the \u03b1-globin locus in human hematopoietic stem cells","volume":"5","author":"Pavani","year":"2021","journal-title":"Blood Adv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41467-017-00479-7","article-title":"Editing an \u03b1-globin enhancer in primary human hematopoietic stem cells as a treatment for \u03b2-thalassemia","volume":"8","author":"Mettananda","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nature00803","article-title":"An abundant erythroid protein that stabilizes free alpha-haemoglobin","volume":"417","author":"Kihm","year":"2002","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Favero, M.E., and Costa, F.F. (2011). Alpha-hemoglobin-stabilizing protein: An erythroid molecular chaperone. Biochem. Res. Int., 2011.","DOI":"10.1155\/2011\/373859"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39016","DOI":"10.1074\/jbc.M506062200","article-title":"GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene","volume":"280","author":"Gallagher","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.exphem.2003.11.002","article-title":"Expression of alpha-hemoglobin stabilizing protein gene during human erythropoiesis","volume":"32","author":"Duarte","year":"2004","journal-title":"Exp. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/10245330500067280","article-title":"AHSP and beta-thalassemia: A possible genetic modifier","volume":"10","author":"Costa","year":"2005","journal-title":"Hematology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/j.1537-2995.2009.02483.x","article-title":"Compensated variability in the expression of globin-related genes in erythroblasts generated ex vivo from different donors","volume":"50","author":"Varricchio","year":"2010","journal-title":"Transfusion"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Han, G., Cao, C., Yang, X., Zhao, G.W., Hu, X.J., Yu, D.L., Yang, R.F., Yang, K., Zhang, Y.Y., and Wang, W.-T. (2022). Nrf2 expands the intracellular pool of the chaperone AHSP in a cellular model of \u03b2-thalassemia. Redox Biol., 50.","DOI":"10.1016\/j.redox.2022.102239"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26956","DOI":"10.1074\/jbc.M802421200","article-title":"An iron responsive element-like stem-loop regulates alpha-hemoglobin-stabilizing protein mRNA","volume":"283","author":"Dore","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1182\/blood-2003-11-3957","article-title":"Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with beta thalassemia","volume":"103","author":"Viprakasit","year":"2004","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ajh.21041","article-title":"Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function","volume":"83","author":"Zhou","year":"2008","journal-title":"Am. J. Hematol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bcmd.2010.04.005","article-title":"Analysis of alpha-hemoglobin-stabilizing protein (AHSP) gene as a genetic modifier to the phenotype of beta-thalassemia in Southern China","volume":"45","author":"Wang","year":"2010","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17986","DOI":"10.1074\/jbc.M109.098491","article-title":"\u03b1-Hemoglobin stabilizing protein (AHSP), a kinetic scheme of the action of a human mutant, AHSPV56G","volume":"285","author":"Brillet","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1007\/s00277-019-03722-x","article-title":"Association of alpha hemoglobin-stabilizing protein (AHSP) gene mutation and disease severity among HbE-beta thalassemia patients","volume":"98","author":"Ray","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1365-2141.2006.06075.x","article-title":"Alpha-haemoglobin stabilising protein is a quantitative trait gene that modifies the phenotype of beta-thalassaemia","volume":"133","author":"Lai","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1375\/twin.13.6.567","article-title":"A twins heritability study on alpha hemoglobin stabilizing protein (AHSP) expression variability","volume":"13","author":"Lai","year":"2010","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1172\/JCI21982","article-title":"Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia","volume":"114","author":"Kong","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_66","first-page":"1881","article-title":"AHSP expression in beta-thalassemia carriers with thalassemia intermedia phenotype","volume":"102","author":"Galanello","year":"2003","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bcmd.2015.07.016","article-title":"Study of alpha hemoglobin stabilizing protein expression in patients with \u03b2 thalassemia and sickle cell anemia and its impact on clinical severity","volume":"55","author":"Mahmoud","year":"2015","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1007\/s12185-019-02806-8","article-title":"Alpha-hemoglobin-stabilizing protein (AHSP): A modulatory factor in \u03b2-thalassemia","volume":"111","author":"Islam","year":"2020","journal-title":"Int. J. Hematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/03630269.2020.1776322","article-title":"Further Characterization of Hb Bronovo [\u03b1103(G10)His\u2192Leu; HBA2: C.311A>T] and First Report of the Homozygous State","volume":"44","author":"Mehta","year":"2020","journal-title":"Hemoglobin"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cardiero, G., Musollino, G., Friscia, M.G., Testa, R., Virruso, L., Di Girgenti, C., Caldora, M., Colella Bisogno, R., Gaudiano, C., and Manco, G. (2020). Effect of Mutations on mRNA and Globin Stability: The Cases of Hb Bernalda\/Groene Hart and Hb Southern Italy. Genes, 11.","DOI":"10.3390\/genes11080870"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Cardiero, G., Musollino, G., Prezioso, R., and Lacerra, G. (2021). mRNA Analysis of Frameshift Mutations with Stop Codon in the Last Exon: The Case of Hemoglobins Campania [\u03b11 cod95 (-C)] and Sciacca [\u03b11 cod109 (-C)]. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101390"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/bjh.17728","article-title":"Alpha haemoglobin-stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment","volume":"196","author":"Vasseur","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1056\/NEJM198206173062402","article-title":"The interaction of alpha-thalassemia and homozygous sickle-cell disease","volume":"306","author":"Higgs","year":"1982","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1056\/NEJM198202043060504","article-title":"Concurrent sickle-cell anemia and alpha-thalassemia: Effect on severity of anemia","volume":"306","author":"Embury","year":"1982","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198307213090320","article-title":"alpha-Thalassemia reduces the hemolytic rate in homozygous sickle-cell disease","volume":"309","author":"Higgs","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2337484","DOI":"10.1001\/jamanetworkopen.2023.37484","article-title":"Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis","volume":"6","author":"Kirkham","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_77","unstructured":"Vichinsky, E. (2024, January 24). Overview of Compound Sickle Cell Syndromes. Available online: https:\/\/medilib.ir\/uptodate\/show\/7115."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"E593","DOI":"10.1002\/ajh.24835","article-title":"Elevated soluble \u03b1-hemoglobin pool in sickle cell anemia","volume":"92","author":"Vasseur","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_79","first-page":"E302","article-title":"Hydroxycarbamide decreases the free alpha-hemoglobin pool in red blood cells of adult patients with sickle cell anemia","volume":"95","author":"Vasseur","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1089\/hum.2009.132","article-title":"Transgenic human alpha-hemoglobin stabilizing protein could partially relieve betaIVS-2-654-thalassemia syndrome in model mice","volume":"21","author":"Wang","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/ajh.21829","article-title":"Analysis of alpha hemoglobin stabilizing protein overexpression in murine \u03b2-thalassemia","volume":"85","author":"Nasimuzzaman","year":"2010","journal-title":"Am. J. Hematol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1196\/annals.1345.013","article-title":"Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia","volume":"1054","author":"Weiss","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Liu, N., Li, P., Zang, S., Liu, Q., Ma, D., Sun, X., and Ji, C. (2015). Novel agent nitidine chloride induces erythroid differentiation and apoptosis in CML cells through c-Myc-miRNAs axis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116880"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/imcb.12686","article-title":"Exploring the anti-inflammatory activity of sulforaphane","volume":"101","author":"Treasure","year":"2023","journal-title":"Immunol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chauhan, W., and Zennadi, R. (2023). Keap1-Nrf2 Heterodimer: A Therapeutic Target to Ameliorate Sickle Cell Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12030740"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1182\/blood-2021-149528","article-title":"IMR-261, a Novel Oral Nrf2 Activator, Induces Fetal Hemoglobin in Human Erythroblasts, Reduces VOCs, and Ameliorates Ineffective Erythropoiesis in Experimental Mouse Models of Sickle Cell Disease and Beta-Thalassemia","volume":"138","author":"Maciel","year":"2021","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1182\/blood-2005-07-2888","article-title":"A global role for EKLF in definitive and primitive erythropoiesis","volume":"107","author":"Hodge","year":"2006","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1128\/MCB.02216-05","article-title":"Alterations in expression and chromatin configuration of the alpha hemoglobin-stabilizing protein gene in erythroid Kruppel-like factor-deficient mice","volume":"26","author":"Pilon","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s11427-014-4652-z","article-title":"Activation of STAT3 stimulates AHSP expression in K562 cells","volume":"57","author":"Cao","year":"2014","journal-title":"Sci. China Life. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.exphem.2007.11.003","article-title":"Reduction of AHSP synthesis in hemin-induced K562 cells and EPO-induced CD34(+) cells leads to alpha-globin precipitation, impairment of normal hemoglobin production, and increased cell death","volume":"36","author":"Pinho","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s43587-021-00098-4","article-title":"Autophagy in healthy aging and disease","volume":"1","author":"Aman","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.blre.2017.04.001","article-title":"Autophagy: A necessary event during erythropoiesis","volume":"31","author":"Grosso","year":"2017","journal-title":"Blood Rev."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Li, J., Quan, C., He, Y.L., Cao, Y., Chen, Y., Wang, Y.F., and Wu, L.Y. (2022). Autophagy regulated by the HIF\/REDD1\/mTORC1 signaling is progressively increased during erythroid differentiation under hypoxia. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.896893"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1182\/bloodadvances.2021005910","article-title":"ATG4A regulates human erythroid maturation and mitochondrial clearance","volume":"6","author":"Stolla","year":"2022","journal-title":"Blood Adv."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"119900","DOI":"10.1016\/j.lfs.2021.119900","article-title":"zmiz1a zebrafish mutants have defective erythropoiesis, altered expression of autophagy genes, and a deficient response to vitamin D","volume":"284","year":"2021","journal-title":"Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/MOH.0000000000000495","article-title":"Oxidation and erythropoiesis","volume":"26","author":"Matte","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Grosso, R.A., Caldarone, P.V.S., S\u00e1nchez, M.C., Chiabrando, G.A., Colombo, M.I., and Fader, C.M. (2019). Hemin induces autophagy in a leukemic erythroblast cell line through the LRP1 receptor. Biosci. Rep., 39.","DOI":"10.1042\/BSR20181156"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.3390\/ijms16024083","article-title":"Autophagy as a regulatory component of erythropoiesis","volume":"16","author":"Zhang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eaav4881","DOI":"10.1126\/scitranslmed.aav4881","article-title":"The autophagy-activating kinase ULK1 mediates clearance of free \u03b1-globin in \u03b2-thalassemia","volume":"11","author":"Lechauve","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18628","DOI":"10.1038\/s41598-022-21249-6","article-title":"Increased autophagy leads to decreased apoptosis during \u03b2-thalassaemic mouse and patient erythropoiesis","volume":"12","author":"Chaichompoo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Chaichompoo, P., Svasti, S., and Smith, D.R. (2022). The Roles of Mitophagy and Autophagy in Ineffective Erythropoiesis in \u03b2-Thalassemia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810811"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s12185-016-2114-z","article-title":"Mitophagy is increased during erythroid differentiation in \u03b2-thalassemia","volume":"105","author":"Wu","year":"2017","journal-title":"Int. J. Hematol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00277-010-1152-5","article-title":"Enhanced activation of autophagy in \u03b2-thalassemia\/Hb E erythroblasts during erythropoiesis","volume":"90","author":"Lithanatudom","year":"2011","journal-title":"Ann. Hematol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5265","DOI":"10.1182\/blood-2011-12-397729","article-title":"Integrated protein quality-control pathways regulate free \u03b1-globin in murine \u03b2-thalassemia","volume":"119","author":"Khandros","year":"2012","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-1-4614-1680-7_11","article-title":"Autophagy and self-defense","volume":"738","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zurlo, M., Gasparello, J., Cosenza, L.C., Breveglieri, G., Papi, C., Zuccato, C., Gambari, R., and Finotti, A. (2023). Production and Characterization of K562 Cellular Clones Hyper-Expressing the Gene Encoding \u03b1-Globin: Preliminary Analysis of Biomarkers Associated with Autophagy. Genes, 14.","DOI":"10.3390\/genes14030556"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1600-0609.2006.00731.x","article-title":"Effects of rapamycin on accumulation of alpha-, beta- and gamma-globin mRNAs in erythroid precursor cells from beta-thalassaemia patients","volume":"77","author":"Fibach","year":"2006","journal-title":"Eur. J. Haematol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"20406207221100648","DOI":"10.1177\/20406207221100648","article-title":"Expression of \u03b3-globin genes in \u03b2-thalassemia patients treated with sirolimus: Results from a pilot clinical trial (Sirthalaclin)","volume":"13","author":"Zuccato","year":"2022","journal-title":"Ther. Adv. Hematol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Zurlo, M., Zuccato, C., Cosenza, L.C., Gasparello, J., Gamberini, M.R., Stievano, A., Fortini, M., Prosdocimi, M., Finotti, A., and Gambari, R. (2023). Decrease of \u03b1-globin and increase of the autophagy-activating kinase ULK1 mRNA in erythroid precursors from \u03b2-thalassemia patients treated with sirolimus. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202309.0170.v1"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1182\/blood.2022017265","article-title":"Loss of miR-144\/451 alleviates \u03b2-thalassemia by stimulating ULK1-mediated autophagy of free \u03b1-globin","volume":"142","author":"Keith","year":"2023","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"E416","DOI":"10.1002\/ajh.26323","article-title":"The International Hemoglobinopathy Research Network (INHERENT): An international initiative to study the role of genetic modifiers in hemoglobinopathies","volume":"96","author":"Kountouris","year":"2021","journal-title":"Am. J. Hematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:01Z","timestamp":1760105701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,17]]},"references-count":112,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063400"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063400","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,17]]}}}