Blood Cells Molecules and Diseases最新文献

{"title":"The inhibitor of MyoD Family A (I-MFA) regulates megakaryocyte lineage commitment and terminal differentiation","authors":"Jeremy S. Houser ,&nbsp;Maulin Patel ,&nbsp;Kyle Wright ,&nbsp;Marta Onopiuk ,&nbsp;Leonidas Tsiokas ,&nbsp;Mary Beth Humphrey","doi":"10.1016/j.bcmd.2023.102760","DOIUrl":"10.1016/j.bcmd.2023.102760","url":null,"abstract":"<div><p><span><span><span>Hematopoiesis<span> and lineage commitment are regulated by several conserved cell-intrinsic </span></span>signaling pathways<span>, including MAPKs and β-catenin/TCF/LEF. The Inhibitor of </span></span>MyoD<span><span><span> Family A (I-MFA), a transcriptional repressor and </span>tumor suppressor gene, interacts with these pathways and is dysregulated in chronic and </span>acute myeloid leukemias<span>, suggesting it may play a role in development and differentiation during hematopoiesis. To study this, immune cell populations in the bone marrow (BM) and periphery were analyzed in mice lacking </span></span></span><em>Mdfi,</em><span> encoding I-MFA (I-MFA−/−), and wild type (WT) controls. I-MFA−/− mice had reduced spleen and BM cellularity, with significant hyposplenism, compared to WT mice. In blood, total red blood cells<span> and platelet counts were significantly reduced in I-MFA−/− mice, accompanied by a reduction in megakaryocyte<span><span><span> (MK)/erythrocyte progenitor cells and an increase in myeloid progenitors in BM compared to WT mice. The K562 cell line exhibits PMA-induced MK differentiation, and </span>shRNA knockdown of I-MFA resulted in reduced differentiation compared to control, with an increase and prolongation in phospho-JNK and phospho-ERK signaling. Overexpression of I-MFA promoted MK differentiation. These results suggest I-MFA plays a cell-intrinsic role in the response to differentiation signals, an effect that can be explored in the context of </span>hematological cancers or other blood proliferative disorders.</span></span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102760"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe clinical picture in a cohort of six Brazilian children with hemoglobin Sβ-thalassemia IVS-I-5 G>A","authors":"Marcos Borato Viana ,&nbsp;Érica Louback Oliveira ,&nbsp;André Rolim Belisário","doi":"10.1016/j.bcmd.2023.102795","DOIUrl":"10.1016/j.bcmd.2023.102795","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102795"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of seven hox genes in zebrafish thrombopoiesis","authors":"Hemalatha Sundaramoorthi,&nbsp;Weam Fallatah,&nbsp;Jabila Mary,&nbsp;Pudur Jagadeeswaran","doi":"10.1016/j.bcmd.2023.102796","DOIUrl":"10.1016/j.bcmd.2023.102796","url":null,"abstract":"<div><p><span><span>Thrombopoiesis is the production of platelets from </span>megakaryocytes<span> in the bone marrow of mammals. In fish, thrombopoiesis involves the formation of thrombocytes without megakaryocyte-like precursors but derived from erythrocyte thrombocyte bi-functional precursor cells. One unique feature of thrombocyte differentiation involves the maturation of young thrombocytes in circulation. In this study, we investigated the role of </span></span><em>hox</em> genes in zebrafish thrombopoiesis to model platelet production. We selected <em>hoxa10b</em>, <em>hoxb2a</em>, <em>hoxc5a</em>, <em>hoxd3a,</em> and <em>hoxc11b</em><span> from thrombocyte RNA expression data, and checked whether they are expressed in young or mature thrombocytes. We found </span><em>hoxa10b</em>, <em>hoxb2a</em>, <em>hoxc5a</em>, and <em>hoxd3a</em> were expressed in both young and mature thrombocytes and <em>hoxc11b</em> was expressed in only young thrombocytes. We then performed knockdowns of these 5 <em>hox</em> genes and found <em>hoxc11b</em><span><span> knockdown resulted in thrombocytosis and the rest showed </span>thrombocytopenia. To identify </span><em>hox</em> genes that could have been missed by the above datasets, we performed knockdowns 47 <em>hox</em> genes in the zebrafish genome and found <em>hoxa9a</em>, and <em>hoxb1a</em> knockdowns resulted in thrombocytopenia and they were expressed in both young and mature thrombocytes. In conclusion, our comprehensive knockdown study identified Hoxa10b, Hoxb2a, Hoxc5a, Hoxd3a, Hoxa9a, and Hoxb1a, as positive regulators and Hoxc11b<em>,</em> as a negative regulator for thrombocyte development.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102796"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome of first or second transplantation using unrelated umbilical cord blood without ATG conditioning regimen for pediatric bone marrow failure disorders","authors":"Xia Chen ,&nbsp;Fang Liu ,&nbsp;Yuanyuan Ren ,&nbsp;Luyang Zhang,&nbsp;Yang Wan,&nbsp;Wenyu Yang,&nbsp;Xiaojuan Chen,&nbsp;Li Zhang,&nbsp;Yao Zou,&nbsp;Yumei Chen,&nbsp;Xiaofan Zhu,&nbsp;Ye Guo","doi":"10.1016/j.bcmd.2023.102793","DOIUrl":"10.1016/j.bcmd.2023.102793","url":null,"abstract":"<div><h3>Background</h3><p><span>Unrelated umbilical cord blood transplantation<span> (UCBT) for bone marrow failure (BMF) disorders using conditioning regimens without Anti-Thymocyte Globulin (ATG) has been used as an alternative transplantation for emerging patients without matched-sibling donors. Experience with this transplant modality in children is limited, especially as a secondary </span></span>treatment for transplant failure patients.</p></div><div><h3>Procedure</h3><p><span><span>We retrospectively reviewed 17 consecutive bone marrow failure patients who underwent unrelated umbilical cord blood transplantation in our center and received conditioning regimens of Total Body Irradiation (TBI) or </span>Busulfan<span> (BU) + Fludarabine (FLU) + </span></span>Cyclophosphamide (CY).</p></div><div><h3>Results</h3><p>Among the 17 BMF patients, 15 patients were treated with first cord blood transplantation and another 2 with secondary cord blood transplantation because of graft failure<span> after first haploidentical stem cell transplantation at days +38 and +82.</span></p><p><span>All patients engrafted with a median donor cell chimerism of 50 % at days +7 (range, 16 %–99.95 %) and finally rose to 100 % at days +30. Median time to neutrophil </span>engraftment<span><span> was 19 days (range, 12–30) and time to platelet engraftment was 32 days (range, 18–61). Pre-engraftment syndrome (PES) was found in 16 patients (94.11 %, 16/17). Cumulative incidence of grades II to IV acute GVHD was 58.8 % (95 % CI: 32.7–84.9 %), and 17.6 % (95 % CI: 2.6–37.9 %) of patients developed </span>chronic GVHD. The 3-year overall survival (OS) and failure-free survival (FFS) rates were 92.86 ± 6.88 %.</span></p></div><div><h3>Conclusion</h3><p>UCBT is an effective alternative treatment for bone marrow failure pediatric patients. TBI/BU + FLU + CY regimen ensure a high engraftment rate for unrelated umbilical cord blood transplantation, which overcomes the difficulty of graft failure. Secondary salvage use of cord blood transplantation may still be useful for patients who have failed after other transplantation.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102793"},"PeriodicalIF":2.3,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10131323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and clinical characterization of two unrelated families with factor V deficiency, including a novel nonsense variant (p.Gln1532*)","authors":"Ke Zhang,&nbsp;Longying Ye,&nbsp;Yanhui Jin,&nbsp;Yuan Chen,&nbsp;Shuting Jiang,&nbsp;Haixiao Xie,&nbsp;Lihong Yang,&nbsp;Mingshan Wang","doi":"10.1016/j.bcmd.2023.102794","DOIUrl":"10.1016/j.bcmd.2023.102794","url":null,"abstract":"<div><h3>Background</h3><p>Factor V (FV) is an essential cofactor in the coagulation cascade. The characterization of novel mutations is advantageous for the clinical management of FV-deficient patients.</p></div><div><h3>Methods</h3><p>Coagulation screening and thrombin generation assay were performed with the plate-poor plasma. All 25 exons of the <em>F5</em><span> gene were amplified and sequenced. The ClustalX-2.1 software was applied to the multiple sequence alignment<span><span>. The possible adverse effects of mutations were investigated with online bioinformatics software and </span>protein modeling.</span></span></p></div><div><h3>Results</h3><p><span><span>Two unrelated families with FV deficiency were under investigation. Proband<span> A was an 18-year-old youth with recurrent epistaxis. Proband B was a 29-year-old woman who did not present with any bleeding symptoms. Three heterozygous mutations (p.Gln1532*, p.Phe218Ser, and p.Asp2222Gly) were detected. Interestingly, they were compound </span></span>heterozygotes and both contained the p.Asp2222Gly, a polymorphism. The thrombin generation assay showed that both patients had impaired ability of thrombin generation, and in particular, proband A was more severe. Conservation, </span>pathogenicity and protein modeling studies all indicated that these three mutations could cause deleterious effects on the function and structure of FV.</p></div><div><h3>Conclusion</h3><p>These three mutations are responsible for the FV-deficient in two pedigrees. Moreover, the nonsense variant p.Gln1532* is first reported in the world.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102794"},"PeriodicalIF":2.3,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bach1 inhibitor HPP-D mediates γ-globin gene activation in sickle erythroid progenitors","authors":"Chithra D. Palani ,&nbsp;Xingguo Zhu ,&nbsp;Manickam Alagar ,&nbsp;Otis C. Attucks ,&nbsp;Betty S. Pace","doi":"10.1016/j.bcmd.2023.102792","DOIUrl":"10.1016/j.bcmd.2023.102792","url":null,"abstract":"<div><p><span><span><span><span>Sickle cell disease (SCD) is the most common β-hemoglobinopathy caused by various mutations in the adult β-globin gene resulting in </span>sickle hemoglobin production, chronic </span>hemolytic anemia<span>, pain, and progressive organ damage. The best therapeutic strategies to manage the clinical symptoms of SCD is the induction of fetal hemoglobin (HbF) using chemical agents. At present, among the Food and Drug Administration-approved </span></span>drugs<span> to treat SCD, hydroxyurea<span><span> is the only one proven to induce HbF protein synthesis, however, it is not effective in all people. Therefore, we evaluated the ability of the novel Bach1 inhibitor, HPP-D to induce HbF in KU812 cells and primary sickle erythroid progenitors. HPP-D increased HbF and decreased Bach1 protein levels in both cell types. Furthermore, </span>chromatin immunoprecipitation assay<span> showed reduced Bach1 and increased NRF2 binding to the γ-globin promoter antioxidant response elements. We also observed increased levels of the active </span></span></span></span>histone<span> marks H3K4Me1 and H3K4Me3 supporting an open chromatin configuration. In primary sickle erythroid progenitors, HPP-D increased γ-globin transcription and HbF positive cells and reduced sickled erythroid progenitors under hypoxia conditions. Collectively, our data demonstrate that HPP-D induces γ-globin gene transcription through Bach1 inhibition and enhanced NRF2 binding in the γ-globin promoter antioxidant response elements.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102792"},"PeriodicalIF":2.3,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10065919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bach1 inhibitor HPP-D mediates γ-globin gene activation in sickle erythroid progenitors.","authors":"C. Palani, Xingguo Zhu, Manickam Alagar, Otis C. Attucks, B. Pace","doi":"10.2139/ssrn.4355763","DOIUrl":"https://doi.org/10.2139/ssrn.4355763","url":null,"abstract":"Sickle cell disease (SCD) is the most common β-hemoglobinopathy caused by various mutations in the adult β-globin gene resulting in sickle hemoglobin production, chronic hemolytic anemia, pain, and progressive organ damage. The best therapeutic strategies to manage the clinical symptoms of SCD is the induction of fetal hemoglobin (HbF) using chemical agents. At present, among the Food and Drug Administration-approved drugs to treat SCD, hydroxyurea is the only one proven to induce HbF protein synthesis, however, it is not effective in all people. Therefore, we evaluated the ability of the novel Bach1 inhibitor, HPP-D to induce HbF in KU812 cells and primary sickle erythroid progenitors. HPP-D increased HbF and decreased Bach1 protein levels in both cell types. Furthermore, chromatin immunoprecipitation assay showed reduced Bach1 and increased NRF2 binding to the γ-globin promoter antioxidant response elements. We also observed increased levels of the active histone marks H3K4Me1 and H3K4Me3 supporting an open chromatin configuration. In primary sickle erythroid progenitors, HPP-D increased γ-globin transcription and HbF positive cells and reduced sickled erythroid progenitors under hypoxia conditions. Collectively, our data demonstrate that HPP-D induces γ-globin gene transcription through Bach1 inhibition and enhanced NRF2 binding in the γ-globin promoter antioxidant response elements.","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 1","pages":"102792"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49536042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic examination of hematological parameters in SARS-CoV-2 infection and COVID-19","authors":"Quan Sun ,&nbsp;Bryce Rowland ,&nbsp;Wanjiang Wang ,&nbsp;Tyne W. Miller-Fleming ,&nbsp;Nancy Cox ,&nbsp;Misa Graff ,&nbsp;Annika Faucon ,&nbsp;Megan M. Shuey ,&nbsp;Elizabeth E. Blue ,&nbsp;Paul Auer ,&nbsp;Yun Li ,&nbsp;Vijay G. Sankaran ,&nbsp;Alexander P. Reiner ,&nbsp;Laura M. Raffield","doi":"10.1016/j.bcmd.2023.102782","DOIUrl":"10.1016/j.bcmd.2023.102782","url":null,"abstract":"<div><p><span><span>People hospitalized with COVID-19 often exhibit altered hematological traits associated with disease prognosis (e.g., lower lymphocyte and platelet counts). We investigated whether inter-individual variability in baseline hematological traits influences risk of acute SARS-CoV-2 infection or progression to severe COVID-19. We report inconsistent associations between blood cell traits with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we also assessed the shared genetic architecture of baseline blood cell traits on COVID-19 related outcomes by </span>Mendelian randomization (MR) analyses. We found significant relationships between COVID-19 severity and mean sphered cell volume after adjusting for multiple testing. However, MR results differed significantly across different freezes of COVID-19 summary statistics and genetic correlation between these traits was modest (0.1), decreasing our confidence in these results. We observed overlapping genetic association signals between other hematological and COVID-19 traits at specific loci such as </span><span><em>MAPT</em></span> and <span><em>TYK2</em></span>. In conclusion, we did not find convincing evidence of relationships between the genetic architecture of blood cell traits and either SARS-CoV-2 infection or COVID-19 hospitalization, though we do see evidence of shared signals at specific loci.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102782"},"PeriodicalIF":2.3,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with mutations inheritance in PIEZO1, Spectrin ß1, RhAG and SLC4A1","authors":"Benoit Allegrini ,&nbsp;Ludivine David NGuyen ,&nbsp;Morgane Mignotet ,&nbsp;Catherine Etchebest ,&nbsp;Odile Fenneteau ,&nbsp;Jessica Platon ,&nbsp;Anne Lambilliotte ,&nbsp;Hélène Guizouarn ,&nbsp;Lydie Da Costa","doi":"10.1016/j.bcmd.2023.102780","DOIUrl":"10.1016/j.bcmd.2023.102780","url":null,"abstract":"<div><p><span><span>We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests confirmed the hemolysis with increased total and indirect bilirubin. The usual hemolysis diagnosis tests were normal (DAT, G6PD, PK, Hb electrophoresis) except </span>cytology<span> and ektacytometry suggesting an association of multiple red blood cell (RBC) membrane disorders. This led us to propose a molecular screening analysis using targeted-Next Generation Sequencing (t-NGS) with a capture technique on 93 genes involved in RBC<span> and erythropoiesis defects. We identified 4 missense heterozygous allelic variations, all of them were described without any significance (VUS) in the </span></span></span><em>SLC4A1</em>, <em>RhAG</em>, <em>PIEZO1</em> and <em>SPTB</em><span> genes. The study of the familial cosegregation and research functional tests allowed to decipher the role of at least two by two genes in the phenotype and the hemolytic disease<span> of this young patient. Specialized t-NGS panel (or virtual exome/genome sequencing) in a disease-referent laboratory and the motivated collaboration of clinicians, biologists and scientists should be the gold standard for improving the diagnosis of the patients affected with RBC diseases or rare inherited anemias.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102780"},"PeriodicalIF":2.3,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10368379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-regulation of microRNA 101-3p during erythropoiesis in β-thalassemia/HbE","authors":"Phatchariya Phannasil ,&nbsp;Chanyanat Sukhuma ,&nbsp;Donny Nauphar ,&nbsp;Khanita Nuamsee ,&nbsp;Saovaros Svasti","doi":"10.1016/j.bcmd.2023.102781","DOIUrl":"10.1016/j.bcmd.2023.102781","url":null,"abstract":"<div><p><span><span>Ineffective erythropoiesis is the main cause of anemia in β-thalassemia. The crucial hallmark of ineffective erythropoiesis is the high proliferation of </span>erythroblast<span>. microRNA<span> (miR/miRNA) involves several biological processes<span>, including cell proliferation and erythropoiesis. miR-101 was widely studied and associated with proliferation in several types of cancer. However, the miR-101-3p has not been studied in β-thalassemia/HbE. Therefore, this study aims to investigate the expression of miR-101-3p during erythropoiesis in β-thalassemia/HbE. The results showed that miR-101-3p was upregulated in the erythroblast of β-thalassemia/HbE patients on day 7, indicating that miR-101-3p may be involved with high proliferation in β-thalassemia/HbE. Therefore, the mRNA targets of miR-101-3p including </span></span></span></span><em>Rac1</em>, <span><em>SUB1</em></span>, <em>TET2</em>, and <em>TRIM44</em> were investigated to determine the mechanisms involved with high proliferation of β-thalassemia/HbE erythroblasts. <em>Rac1</em> expression was significantly reduced at day 11 in severe β-thalassemia/HbE compared to normal controls and mild β-thalassemia/HbE. <em>SUB1</em> gene expression was significantly lower in severe β-thalassemia/HbE compared to normal controls at day 9 of culture. For TET2 and TRIM44 expression, a significant difference was not observed among normal and β-thalassemia/HbE. However, the high expression of miR-101-3p at day 7 and these target genes was not correlated, suggesting that this miRNA may regulate ineffective erythropoiesis in β-thalassemia/HbE via other target genes.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"103 ","pages":"Article 102781"},"PeriodicalIF":2.3,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}