Blood Cells Molecules and Diseases最新文献

{"title":"Clonal hematopoiesis and acquired genetic abnormalities of the red cell: An historical review","authors":"Marshall A. Lichtman","doi":"10.1016/j.bcmd.2023.102801","DOIUrl":"10.1016/j.bcmd.2023.102801","url":null,"abstract":"<div><p>Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These syndromes are most notable in cases of myelodysplastic syndrome, but they are not limited to any one category of myeloid neoplasm. Their occurrence in males exceed the male predominance that is evident in myeloid neoplasms. The syndromes include disorders of globin chain synthesis (α- and β-thalassemia), heme synthesis (erythropoietic porphyria and erythropoietic uroporphyria), red cell membrane structure (elliptocytosis and spherocytosis), red cell enzyme activity (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency) and lowered expression of red cell ABO blood group antigens. This historical review describes the path to uncovering these acquired syndromes and their causal somatic mutations, where known. These syndromes often go unrecognized because of the dominant concern of the primary neoplasm. They may add to the healthcare needs of the patient.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102801"},"PeriodicalIF":2.3,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716868","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":"Calcium flux alterations in erythrocytes from sickle cell mice: The relevance of mean corpuscular volume","authors":"Luis E.F. Almeida,&nbsp;Meghann L. Smith,&nbsp;Sayuri Kamimura,&nbsp;Sebastian Vogel,&nbsp;Zenaide M.N. Quezado","doi":"10.1016/j.bcmd.2023.102800","DOIUrl":"10.1016/j.bcmd.2023.102800","url":null,"abstract":"<div><p>Red blood cells (RBC) from patients with sickle cell disease (SCD) have elevated calcium levels at baseline, which are further elevated upon deoxygenation. Here we examined baseline calcium levels and calcium flux in RBCs from a mouse model of SCD mice. We found that akin to humans with SCD, sickle (HbSS) Townes mice, have higher baseline levels and increased calcium flux in RBCs compared to control (HbAA) animals. As HbSS mice, unlike humans with SCD, have high mean corpuscular volume compared with HbAA, we highlight the importance of adjusting biochemical results to number of RBCs rather than hematocrit during the analysis and interpretation of the results. Our findings add to the face validity of humanized sickle cell mice and support its use for studies of RBC calcium flux in SCD.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102800"},"PeriodicalIF":2.3,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716867","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":"Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells","authors":"Natália Sudan Parducci ,&nbsp;Anali Del Milagro Bernabe Garnique ,&nbsp;Keli Lima ,&nbsp;Jorge Antonio Elias Godoy Carlos ,&nbsp;Natasha Peixoto Fonseca ,&nbsp;Lívia Bassani Lins de Miranda ,&nbsp;Bruna Oliveira de Almeida ,&nbsp;Eduardo Magalhães Rego ,&nbsp;Fabiola Traina ,&nbsp;João Agostinho Machado-Neto","doi":"10.1016/j.bcmd.2023.102799","DOIUrl":"https://doi.org/10.1016/j.bcmd.2023.102799","url":null,"abstract":"<div><p><span>Myeloproliferative neoplasms<span><span> (MPN) are consolidated as a relevant group of diseases<span> derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid </span></span>lineage<span>. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the </span></span></span><em>CSF3R</em><span> gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2</span>^V617F<span> increased the expression of the aurora kinase A<span> (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2</span></span>^V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3R^T618I<span>-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R</span>^T618I<span><span><span><span><span> mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, </span>clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced </span>histone H3<span> phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced </span></span>PARP1<span> cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other </span></span>drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102799"},"PeriodicalIF":2.3,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49821171","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":"The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia","authors":"Fanbi Meng ,&nbsp;Shuang Chen ,&nbsp;Chunliang Liu ,&nbsp;Muhammad Shoaib Khan,&nbsp;Yan Yan,&nbsp;Jun Wan,&nbsp;Yue Xia,&nbsp;Chenglin Sun,&nbsp;Mengnan Yang,&nbsp;Renping Hu,&nbsp;Kesheng Dai","doi":"10.1016/j.bcmd.2023.102798","DOIUrl":"10.1016/j.bcmd.2023.102798","url":null,"abstract":"<div><p><span>Thrombocytopenia<span> is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte<span><span> development and platelet production<span> are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. </span></span>Protein kinase C<span> (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis<span><span><span>. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced </span>mitochondrial membrane potential and </span>ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. </span></span></span></span></span><em>In vivo</em><span> experiments confirmed that Go6983 promoted platelet count<span><span> recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and </span>polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102798"},"PeriodicalIF":2.3,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182019","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":"First report of a patient with homozygous hemoglobin Ernz: Evidence to support a non-pathogenic variant","authors":"Zohreh Shojaei ,&nbsp;Maryam Abiri ,&nbsp;Fatemeh Zafarghandi Motlagh ,&nbsp;Masoume Amini ,&nbsp;Samira Dabbagh Bagheri ,&nbsp;Sadaf Asnavandi ,&nbsp;Sedighe Asadi ,&nbsp;Hamideh Bagherian ,&nbsp;Sirous Zeinali","doi":"10.1016/j.bcmd.2023.102797","DOIUrl":"10.1016/j.bcmd.2023.102797","url":null,"abstract":"<div><p>Hemoglobin Ernz (Hb Ernz) is a missense variant in β-globin caused by a Threonine<span><span> to Asparagine substitution at the 123rd </span>amino acid<span><span> position and HBB c.371C &gt; A in gene level. Hb Ernz has been classified as Uncertain Significance (VUS) by ACMG due to limited reports and the absence of any homozygote<span> genotypes. In our study, we found eight cases of Hb Ernz by DNA sequencing of the β-globin gene during &gt;20 years of </span></span>Thalassemia Screening in individuals with borderline hematological parameters who were possible carriers of thalassemia or their spouses. We also report the first homozygote variant of Hb Ernz. Our findings suggest that the changes in hematological parameters observed in individuals with Hb Ernz are likely due to α-globin gene mutations rather than Hb Ernz itself. These findings support the reclassification of Hb Ernz as a benign variant in variant classification.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"104 ","pages":"Article 102797"},"PeriodicalIF":2.3,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190220","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":"Targeting of Calbindin 1 rescues erythropoiesis in a human model of Diamond Blackfan anemia","authors":"Nan Wang ,&nbsp;Corinne LaVasseur ,&nbsp;Rao Riaz ,&nbsp;Julien Papoin ,&nbsp;Lionel Blanc ,&nbsp;Anupama Narla","doi":"10.1016/j.bcmd.2023.102759","DOIUrl":"10.1016/j.bcmd.2023.102759","url":null,"abstract":"<div><p><span>Diamond Blackfan anemia<span><span> (DBA) is an inherited bone marrow failure syndrome<span> characterized by congenital anomalies<span>, cancer predisposition and a severe hypo-proliferative anemia. It was the first disease linked to ribosomal dysfunction and &gt;70 % of patients have been identified to have a </span></span></span>haploinsufficiency<span> of a ribosomal protein (RP) gene, with </span></span></span><em>RPS19</em><span><span><span> being the most common mutation. There is significant variability within the disease in terms of phenotype as well as response to therapy suggesting that other genes contribute to the pathophysiology and potential management of this disease. To explore these questions, we performed a genome-wide </span>CRISPR screen in a </span>cellular model<span> of DBA and identified Calbindin 1<span> (CALB1), a member of the calcium-binding superfamily, as a potential modifier of the disordered erythropoiesis in DBA. We used human derived CD34+ cells cultured in erythroid stimulating media with knockdown of </span></span></span><em>RPS19</em> as a model for DBA to study the effects of CALB1. We found that knockdown of CALB1 in this DBA model promoted erythroid maturation. We also noted effects of CALB1 knockdown on cell cycle. Taken together, our results reveal CALB1 is a novel regulator of human erythropoiesis and has implications for using CALB1 as a novel therapeutic target in DBA.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102759"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769247","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":"Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race","authors":"Jennifer K. Frediani ,&nbsp;Ezra Pak-Harvey ,&nbsp;Richard Parsons ,&nbsp;Adrianna L. Westbrook ,&nbsp;William O'Sick ,&nbsp;Greg S. Martin ,&nbsp;Wilbur A. Lam ,&nbsp;Joshua M. Levy","doi":"10.1016/j.bcmd.2023.102756","DOIUrl":"10.1016/j.bcmd.2023.102756","url":null,"abstract":"<div><p>Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (<em>n</em> = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (&lt;16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), <em>P</em> = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), <em>P</em> = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102756"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659326","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":"Two new mutations in the GLRX5 gene cause sideroblastic anemia","authors":"Andrés Felipe Melo Arias,&nbsp;Silvia Escribano Serrat,&nbsp;Jorge Martínez Nieto,&nbsp;Fiorella Medina Salazar,&nbsp;Paloma Ropero Gradilla,&nbsp;Celina Benavente Cuesta,&nbsp;Fernando Ataúlfo González Fernández","doi":"10.1016/j.bcmd.2023.102763","DOIUrl":"10.1016/j.bcmd.2023.102763","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102763"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041805","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":"The utility of multiple genomic technologies for interpretation of modern next generation sequencing: A novel case of three FANCA gene variants resulting in autosomal recessive Fanconi anaemia","authors":"J. Coleman ,&nbsp;A.J. Green ,&nbsp;L. Bradley","doi":"10.1016/j.bcmd.2023.102762","DOIUrl":"10.1016/j.bcmd.2023.102762","url":null,"abstract":"<div><p><span>Fanconi anaemia<span><span> (FA) is a rare autosomal recessive condition resulting in changes in the FANC </span>gene family<span>. This report describes a case of Fanconi anaemia in a family with complex biallelic variants. The patient is a 32-year-old female diagnosed with FA on cascade testing during childhood with chromosome breakage<span> studies. On examination she had a fixed deformity of the right thumb and the proximal interphalangeal joint<span> was immobile. Her brother shared this radial abnormality and had FA, requiring a bone marrow transplant. She presented in adulthood seeking further </span></span></span></span></span><em>BRCA</em><span> advice and had next generation sequencing that showed three variants in the </span><span><em>FANCA</em></span> gene. One allele a known pathogenic change, the other had two sequence variants in tandem that have been reported as variants of uncertain significance. There is one other unrelated case of these two variants occurring together in cis, resulting in Fanconi anaemia. This case is an interesting example of three variants in the <em>FANCA</em><span> gene, one allele with a pathogenic deletion and the other with a single complex allele made up of two missense variants of uncertain significance, likely manifesting with FA. It highlights the utility of different genetic technologies in the interpretation of next generation sequencing.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102762"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9721520","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":"Drinking recommended daily water significantly alters haemato-biochemical parameters in prospective blood donors; a one-center quasi-experimental study in a tropical setting","authors":"Bright Kekeli Gbadago ,&nbsp;Juliet Antiaye ,&nbsp;Joseph Boachie ,&nbsp;Patrick Adu","doi":"10.1016/j.bcmd.2023.102757","DOIUrl":"10.1016/j.bcmd.2023.102757","url":null,"abstract":"<div><h3>Background</h3><p>In sub-Saharan Africa, the prevailing high ambient temperatures should warrant increased daily water intake (DWI) to prevent haemo-concentration and its potential to confound patients' laboratory data.</p></div><div><h3>Aim</h3><p>To assess the impact that the recommended DWI has on the haemato-biochemical variables in a tropical setting.</p></div><div><h3>Materials and methods</h3><p>This quasi-experimental study recruited 101 apparently healthy individuals (18–60 years) in the Bawku municipality. DWI, anthropometrics, and haemato-biochemical variables were assessed at baseline. Participants were encouraged to increase their DWI to ≥4 L over a 30-day period; haemato-biochemical variables were re-evaluated. Total body water (TBW) was anthropometrically estimated.</p></div><div><h3>Results</h3><p><span>The median post-treatment DWI significantly increased; consequently, anaemia cases increased by &gt;20-fold (2.0 % vs 47.5 % post-treatment). RBC<span> count, platelet count<span>, WBC count, and median haemoglobin significantly decreased compared to baseline (</span></span></span><em>p</em><span><span><span> &lt; 0.0001). Biochemically, median plasma osmolality (p &lt; 0.0001), </span>serum sodium (p &lt; 0.0001), </span>serum potassium (</span><em>p</em><span> = 0.0012) and random blood sugar (</span><em>p</em><span><span> = 0.0403) significantly decreased. Compared to baseline, significantly higher proportion of participants classified as thrombocytopenic (8.9 % vs 3.0 %), hyponatraemia (10.9 % vs 2.0 %), or normal </span>osmolarity (77.2 % vs 20.8 %). There were differential bivariate correlations between pre- and post-treatment haemato-biochemical variables.</span></p></div><div><h3>Conclusion</h3><p>Sub-optimal DWI is a likely confounder in haemato-biochemical data interpretation in the tropics.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"102 ","pages":"Article 102757"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667141","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}