{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:43:59Z","timestamp":1790765039675,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2017RKWNJT to M.Y.F. -  PRIN 201799WCRH TO L.M."],"award-info":[{"award-number":["PRIN 2017RKWNJT to M.Y.F. -  PRIN 201799WCRH TO L.M."]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione del Monte di Bologna e Ravenna, Italy","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and \u03b2-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or \u03b2-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-\u03b2, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoiesis. Also small mother against decapentaplegic (SMAD) signaling molecules play a role in pathology, and activin receptor ligand traps are being investigated for future clinical applications. Even inositide-dependent signaling, which is important in the regulation of cell proliferation and differentiation, is specifically associated with erythropoiesis, with phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K) as key players that are becoming increasingly important as new promising therapeutic targets. Additionally, Roxadustat, a new erythropoiesis stimulating agent targeting hypoxia inducible factor (HIF), is under clinical development. Here, we review the role and function of the above-mentioned signaling pathways, and we describe the state of the art and new perspectives of erythropoiesis regulation in MDS and \u03b2-thalassemia.<\/jats:p>","DOI":"10.3390\/ijms22020827","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T12:44:05Z","timestamp":1610714645000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and \u03b2-Thalassemia"],"prefix":"10.3390","volume":"22","author":[{"given":"Sarah","family":"Parisi","sequence":"first","affiliation":[{"name":"Department of Oncology and Hematology, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine DIMES, Institute of Hematology \u201cL. and A. Ser\u00e0gnoli\u201d, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Finelli","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine DIMES, Institute of Hematology \u201cL. and A. Ser\u00e0gnoli\u201d, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Fazio","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mongiorgi","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-5345","authenticated-orcid":false,"given":"Stefano","family":"Ratti","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-9072","authenticated-orcid":false,"given":"Anna Maria","family":"Billi","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-8277","authenticated-orcid":false,"given":"Lucio","family":"Cocco","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde Y.","family":"Follo","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Manzoli","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s10020-018-0011-z","article-title":"Erythropoiesis: Insights into pathophysiology and treatments in 2017","volume":"24","author":"Zivot","year":"2018","journal-title":"Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.3324\/haematol.2018.192518","article-title":"Normal and pathological erythropoiesis in adults: From gene regulation to targeted treatment concepts","volume":"103","author":"Valent","year":"2018","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1182\/blood-2014-12-618090","article-title":"TGF-\u03b2 signaling in the control of hematopoietic stem cells","volume":"125","author":"Blank","year":"2015","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.exphem.2008.08.003","article-title":"Erythropoietins: A common mechanism of action","volume":"36","author":"Elliott","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/nrm2297","article-title":"TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility","volume":"8","author":"Schmierer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a022095","DOI":"10.1101\/cshperspect.a022095","article-title":"Regulation of TGF-\u03b2 Family Signaling by Inhibitory Smads","volume":"9","author":"Miyazawa","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0301-472X(00)00488-4","article-title":"Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors","volume":"28","author":"Zermati","year":"2000","journal-title":"Exp. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1002\/jcb.25233","article-title":"Cooperative Effect of Erythropoietin and TGF-\u03b2 Inhibition on Erythroid Development in Human Pluripotent Stem Cells","volume":"116","author":"Xie","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1182\/blood-2007-08-078139","article-title":"Myelodysplastic syndromes","volume":"111","author":"Nimer","year":"2008","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/bjh.14215","article-title":"Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts","volume":"174","author":"Malcovati","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.leukres.2016.02.011","article-title":"SF3B1-mutated myelodysplastic syndrome with ring sideroblasts harbors more severe iron overload and corresponding over-erythropoiesis","volume":"44","author":"Zhu","year":"2016","journal-title":"Leuk. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1172\/JCI133678","article-title":"Biological basis for efficacy of activin receptor ligand traps in myelodysplastic syndromes","volume":"130","author":"Verma","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1182\/blood-2008-02-139824","article-title":"Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in MDS","volume":"112","author":"Zhou","year":"2008","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1158\/0008-5472.CAN-10-2933","article-title":"Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase","volume":"71","author":"Zhou","year":"2011","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1182\/blood-2006-02-005611","article-title":"Smad7 promotes self-renewal of hematopoietic stem cells","volume":"108","author":"Blank","year":"2006","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6976","DOI":"10.1158\/1078-0432.CCR-19-1338","article-title":"Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes","volume":"25","author":"Santini","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1182\/blood-2011-12-397067","article-title":"miR-21 mediates hematopoietic suppression in MDS by activating TGF-\u03b2 signaling","volume":"121","author":"Bhagat","year":"2013","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1172\/JCI66005","article-title":"Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity","volume":"124","author":"Velu","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/MOH.0b013e32832990a4","article-title":"Ineffective erythropoiesis and thalassemias","volume":"16","author":"Rivella","year":"2009","journal-title":"Curr. Opin. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1358\/dot.2020.56.7.3159184","article-title":"Luspatercept to treat \u03b2-thalassemia","volume":"56","author":"Pilo","year":"2020","journal-title":"Drugs Today"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/bjh.13820","article-title":"Ineffective erythropoiesis and regulation of iron status in iron loading anaemias","volume":"172","author":"Camaschella","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s11899-016-0347-9","article-title":"Activin Receptor II Ligand Traps and Their Therapeutic Potential in Myelodysplastic Syndromes with Ring Sideroblasts","volume":"11","author":"Mies","year":"2016","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s11899-019-00517-9","article-title":"Activin Receptor II Ligand Traps: New Treatment Paradigm for Low-Risk MDS","volume":"14","author":"Komrokji","year":"2019","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10792","DOI":"10.1074\/jbc.M115.713487","article-title":"Transforming Growth Factor-\u03b2 Family Ligands Can Function as Antagonists by Competing for Type II Receptor Binding","volume":"291","author":"Aykul","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nm.3512","article-title":"Transforming growth factor-\u03b2 superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis","volume":"20","author":"Suragani","year":"2014","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21037","DOI":"10.1074\/jbc.M110.114959","article-title":"Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIb","volume":"285","author":"Sako","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1182\/blood-2013-06-511238","article-title":"Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine \u03b2-thalassemia","volume":"123","author":"Suragani","year":"2014","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/nm.3468","article-title":"An activin receptor IIA ligand trap corrects ineffective erythropoiesis in \u03b2-thalassemia","volume":"20","author":"Dussiot","year":"2014","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1359\/jbmr.081208","article-title":"Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women","volume":"24","author":"Ruckle","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/jcph.160","article-title":"Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women","volume":"53","author":"Sherman","year":"2013","journal-title":"J. Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/ajh.23732","article-title":"A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers","volume":"89","author":"Attie","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/bjh.12835","article-title":"Sotatercept in patients with osteolytic lesions of multiple myeloma","volume":"165","author":"Abdulkadyrov","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00520-015-2929-9","article-title":"Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: Results from two phase 2 studies","volume":"24","author":"Raftopoulos","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2020075","DOI":"10.4084\/mjhid.2020.075","article-title":"Activin Receptor-Ligand Trap for the Treatment of \u03b2-thalassemia: A Serendipitous Discovery","volume":"12","author":"Brancaleoni","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1016\/S2352-3026(18)30002-4","article-title":"Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: A phase 2, dose-ranging trial","volume":"5","author":"Komrokji","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/S1470-2045(17)30615-0","article-title":"Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): A multicentre, open-label phase 2 dose-finding study with long-term extension study","volume":"18","author":"Platzbecker","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa1908892","article-title":"Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes","volume":"382","author":"Fenaux","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1182\/blood-2018-10-879247","article-title":"Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with \u03b2-thalassemia","volume":"133","author":"Piga","year":"2019","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1056\/NEJMoa1910182","article-title":"A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent \u03b2-Thalassemia","volume":"382","author":"Cappellini","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0145-2126(96)00002-1","article-title":"Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes","volume":"20","author":"Mittelman","year":"1996","journal-title":"Leuk. Res."},{"key":"ref_42","first-page":"466","article-title":"Erythropoiesis in myelodysplastic syndrome: Expression of receptors for erythropoietin and kit ligand","volume":"10","author":"Backx","year":"1996","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1182\/blood.V89.5.1690","article-title":"Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome","volume":"89","author":"Hoefsloot","year":"1997","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-pathol-011110-130321","article-title":"The HIF pathway and erythrocytosis","volume":"6","author":"Lee","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.1111\/hdi.12567","article-title":"HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism","volume":"21","author":"Haase","year":"2017","journal-title":"Hemodial. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1007\/s12325-017-0508-9","article-title":"A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat","volume":"34","author":"Becker","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/ndt\/gfv302","article-title":"Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients","volume":"30","author":"Besarab","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1053\/j.ajkd.2015.12.020","article-title":"Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study","volume":"67","author":"Provenzano","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1681\/ASN.2015030241","article-title":"Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients","volume":"27","author":"Besarab","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMoa1813599","article-title":"Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis","volume":"381","author":"Chen","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_51","first-page":"843","article-title":"Chromatin phospholipids in normal and chronic lymphocytic leukemia lymphocytes","volume":"37","author":"Manzoli","year":"1977","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Obeng, E.O., Rusciano, I., Marvi, M.V., Fazio, A., Ratti, S., Follo, M.Y., Xian, J., Manzoli, L., Billi, A.M., and Mongiorgi, S. (2020). Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072581"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jbior.2013.11.003","article-title":"Nuclear PI-PLCbeta1: An appraisal on targets and pathology","volume":"54","author":"Follo","year":"2014","journal-title":"Adv. Biol. Regul."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2174\/1389557514666141013125936","article-title":"Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy","volume":"14","author":"Manzoli","year":"2014","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1517\/14728222.2016.1125885","article-title":"Inositide-dependent signaling pathways as new therapeutic targets in myelodysplastic syndromes","volume":"20","author":"Mongiorgi","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Xian, J., Obeng, E.O., Ratti, S., Rusciano, I., Marvi, M.V., Fazio, A., De Stefano, A., Mongiorgi, S., Cappellini, A., and Ramazzotti, G. (2020). Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes. Cells, 9.","DOI":"10.3390\/cells9030697"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.2174\/1381612822666160226132338","article-title":"Selective Activation of Nuclear PI-PLCbeta1 During Normal and Therapy-Related Differentiation","volume":"22","author":"Mongiorgi","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/leu.2012.133","article-title":"Activation of nuclear inositide signalling pathways during erythropoietin therapy in low-risk MDS patients","volume":"26","author":"Follo","year":"2012","journal-title":"Leukemia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1096\/fj.201700690R","article-title":"Nuclear translocation of PKC-alpha is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs)","volume":"32","author":"Poli","year":"2018","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exphem.2020.07.006","article-title":"Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and-independent contexts","volume":"88","author":"Estienne","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100664","DOI":"10.1016\/j.jbior.2019.100664","article-title":"Phosphatidylinositol 3 monophosphate metabolizing enzymes in blood platelet production and in thrombosis","volume":"75","author":"Bellio","year":"2020","journal-title":"Adv. Biol. Regul."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1182\/blood-2018-11-876888","article-title":"Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis","volume":"133","author":"Fenaux","year":"2019","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/s41375-019-0448-2","article-title":"Transforming growth factor (TGF)-\u03b2 pathway as a therapeutic target in lower risk myelodysplastic syndromes","volume":"33","author":"Bewersdorf","year":"2019","journal-title":"Leukemia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"106430","DOI":"10.1016\/j.leukres.2020.106430","article-title":"Myelo-deception: Luspatercept & TGF-Beta ligand traps in myeloid diseases & anemia","volume":"97","author":"Feld","year":"2020","journal-title":"Leuk. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/827\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:11:41Z","timestamp":1760159501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,15]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020827"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020827","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,15]]}}}