Blood Cells Molecules and Diseases最新文献

Culprit or innocent bystander? The case of a new fast-moving hemoglobin J variant in a pregnant woman

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2025-03-12 DOI: 10.1016/j.bcmd.2025.102920

Ilaria Cerroni , Valeria Renola , Alessia Micalizzi , Ester Romanelli , Lucrezia De Marchi , Giorgia Ranucci , Flavia Mallegni , Elisa Meddi , Federico Moretti , Camilla Page , Antonietta Viola , Giovangiacinto Paterno , Maria Ilaria Del Principe , Stefania Casciani , Adriano Venditti , Sergio Bernardini , Antonio Novelli , Maria Teresa Voso , Carmelo Gurnari

引用次数: 0

Unveiling the role of RPS17 and SLC4A1 in diamond-Blackfan Anemia: A zebrafish-based study

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2025-02-25 DOI: 10.1016/j.bcmd.2025.102912

Kyeongmin Kim , Hyerin Lee , Soyul Ahn , Yun Hak Kim , Chang-Kyu Oh

{"title":"Unveiling the role of RPS17 and SLC4A1 in diamond-Blackfan Anemia: A zebrafish-based study","authors":"Kyeongmin Kim , Hyerin Lee , Soyul Ahn , Yun Hak Kim , Chang-Kyu Oh","doi":"10.1016/j.bcmd.2025.102912","DOIUrl":"10.1016/j.bcmd.2025.102912","url":null,"abstract":"<div><div>Diamond-Blackfan Anemia (DBA) is a rare congenital disorder characterized by macrocytic anemia, physical abnormalities, and growth delays. Although RPS19 mutations have been more extensively studied in DBA compared to other ribosomal protein genes, the pathological mechanisms of genes such as RPS17 remain largely unexplored. This study aimed to investigate the role of RPS17 haploinsufficiency in DBA, focusing on its downstream effects on erythropoiesis and the involvement of SLC4A1, a critical erythrocyte membrane protein essential for red blood cell stability. Transcriptomic analysis of publicly available RNA sequencing data from DBA patients revealed significant downregulation of SLC4A1 in RPS17-mutated cases. To validate these findings, we generated a zebrafish model of DBA by knocking down <em>rps17</em> using morpholino injections. Zebrafish embryos with <em>rps17</em> knockdown exhibited reduced erythropoiesis, impaired hemoglobin synthesis, consistent with DBA. Further analysis confirmed decreased <em>slc4a1a</em> expression in rps17-morphants. Independent knockdown of <em>slc4a1a</em> in zebrafish resulted in similar erythropoietic defects, highlighting its critical role in red blood cell membrane integrity and function. This study identifies slc4a1 as a key downstream target of RPS17 haploinsufficiency and provides novel insights into the molecular mechanisms of DBA. By establishing zebrafish as an effective in vivo model, this research offers potential therapeutic targets for treating DBA and related erythropoietic disorders.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"112 ","pages":"Article 102912"},"PeriodicalIF":2.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487929","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}

引用次数: 0

Hereditary disorders of ineffective erythropoiesis

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2025-02-07 DOI: 10.1016/j.bcmd.2025.102910

Richard A. King , Rami Khoriaty

引用次数: 0

Immunodeficiency in children with Diamond Blackfan and Diamond Blackfan like anemia

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2025-02-07 DOI: 10.1016/j.bcmd.2025.102911

Iman Ragab , Sara Makkeyah , Noura Hassan , Michael Botros , Lydie Da Costa , Nihal Hussien Aly

{"title":"Immunodeficiency in children with Diamond Blackfan and Diamond Blackfan like anemia","authors":"Iman Ragab , Sara Makkeyah , Noura Hassan , Michael Botros , Lydie Da Costa , Nihal Hussien Aly","doi":"10.1016/j.bcmd.2025.102911","DOIUrl":"10.1016/j.bcmd.2025.102911","url":null,"abstract":"<div><h3>Background</h3><div>Diamond-Blackfan anemia Syndrome (DBAS) is a ribosomopathy with erythroid failure. DBA-like picture occurs with non-ribosomal mutation and a normal rRNA maturation. Immunodeficiency in patients with DBAS is not adequately studied. We aimed to study the frequency of infections and immunoglobulins levels in children with DBAS.</div></div><div><h3>Methods</h3><div>Children and adolescents with DBAS were included. Infections were scored according to the immunodeficiency related score (IDR). Total serum immunoglobulin A (IgA), IgG and IgM were measured. Molecular studies were done to a group of patients.</div></div><div><h3>Results</h3><div>Thirty-four patients had a median age at diagnosis of 3.6 month-old. Fourteen (41 %) patients had an IDR score of ≥6, and 4 of them (28.6 %) had low immunoglobulin levels. Patients with IDR score > 6 had significantly lower IgG (471 versus 1057 mg/dl, <em>p</em> <em>=</em> 0,032) and serum IgA (24 versus 98.5 mg/dl, <em>p</em> <em>=</em> 0.015) than IDR < 6 group. We report mortality in 8 (23.5 %) patients, two of them were related to infection. Molecular analyses were performed in 8 probands and 17 relatives (5 families); 7 of the probands carried <em>CECR1/ADA2</em> gene mutation and one patient carried a pathogenic variant in <em>RPL36</em> gene.</div></div><div><h3>Conclusion</h3><div>We highlight the presence of underlying immunodeficiency in a group of patients with DBA and DBA-like disease.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"111 ","pages":"Article 102911"},"PeriodicalIF":2.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350160","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}

引用次数: 0

Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models – Of mice and men 汤斯和伯克利镰状细胞病小鼠模型中的红细胞丙酮酸激酶特性-小鼠和男性

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2025-01-16 DOI: 10.1016/j.bcmd.2025.102909

Marissa J.M. Traets , Titine J.J. Ruiter , Charles Levine , Anita W. Rijneveld , Judith J. Jans , Carsten Alt , Minke A.E. Rab , Yu-Wei Chen , Richard van Wijk , Brigitte A. van Oirschot

{"title":"Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models – Of mice and men","authors":"Marissa J.M. Traets , Titine J.J. Ruiter , Charles Levine , Anita W. Rijneveld , Judith J. Jans , Carsten Alt , Minke A.E. Rab , Yu-Wei Chen , Richard van Wijk , Brigitte A. van Oirschot","doi":"10.1016/j.bcmd.2025.102909","DOIUrl":"10.1016/j.bcmd.2025.102909","url":null,"abstract":"<div><div>Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties. This study revealed important distinctions with humans (SCD vs healthy controls), such as similar PK/hexokinase (HK) ratios between sickling and non-sickling mouse models and significantly lower PK thermostability in mice. We additionally investigated the effect of a novel RBC PK activator, compound A, on PK properties and sickling tendency in these mice in order to assess SCD mouse model suitability. Results showed that a single dose of compound A led to an increased affinity of PK for phosphoenolpyruvate, a significant increase in PK/HK ratio and a decrease of 2,3-DPG levels. Together, these results offer detailed characterization in the PK properties of two commonly used SCD mouse models, and provide insight into the mode of action of PK activator therapy in SCD mice models.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"111 ","pages":"Article 102909"},"PeriodicalIF":2.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999414","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}

引用次数: 0

Short- and long-term alterations of hematopoietic cell lineages in rats with congenital iron deficiency 先天性缺铁大鼠造血细胞谱系的短期和长期改变。

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2024-12-17 DOI: 10.1016/j.bcmd.2024.102908

Anthony Babu , Zachary R. Smith , Narmin Mukhtarova , Ashajyothi M. Siddappa , Pamela J. Kling

{"title":"Short- and long-term alterations of hematopoietic cell lineages in rats with congenital iron deficiency","authors":"Anthony Babu , Zachary R. Smith , Narmin Mukhtarova , Ashajyothi M. Siddappa , Pamela J. Kling","doi":"10.1016/j.bcmd.2024.102908","DOIUrl":"10.1016/j.bcmd.2024.102908","url":null,"abstract":"<div><div>Data support that fetal iron delivery is prioritized to hemoglobin in erythrocytes (RBC). Iron deficiency (ID) during pregnancy can cause congenital ID, i.e., low fetal iron acquisition. Because how congenital ID impacts other fetal hematopoietic cell lineages is unknown our pilot study examined this in a rat congenital ID model. Pregnant dams fed ID diets were compared to iron sufficient (IS) controls. Iron indices, complete cell counts with differentials, and microscopic morphology were studied at birth P2–3, mid-recovery P15 and adolescent post-recovery P45. Compared to IS at birth, ID rats exhibited 350 % higher zinc protoporphyrin/heme, 70 % lower plasma ferritin, 30 % lower hemoglobin, 25 % fewer platelets, but nucleated RBC (nRBC) and reticulocytes did not differ. Compared to IS at birth, ID rats exhibited 36 % fewer white counts (WBC) but proportionate lymphocytes and granulocytes (all <em>P</em> < 0.015). Compared to IS at P45, RBC, platelets, and WBC numbers did not differ, but lymphocytes were relatively lower in ID (<em>P</em> < 0.01). Microscopic morphology differed from IS in ID, with persistent differences at P45. Because altered inflammatory programming was previously reported in congenital ID and because this pilot study found altered WBC populations, this model of congenital ID is well situated to investigate long-term developmental programming.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"111 ","pages":"Article 102908"},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871124","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}

引用次数: 0

Corrigendum to “Clinical utility of relative telomere length analysis in pediatric bone marrow failure” [Blood Cells Mol. Dis. 109 (2024) 102882] 更正："相对端粒长度分析在小儿骨髓衰竭中的临床应用" [Blood Cells Mol. Dis. 109 (2024) 102882]。

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2024-11-07 DOI: 10.1016/j.bcmd.2024.102899

Shilpa Amatya , Prateek Bhatia , Sudhanshi Raina , Sreejesh Sreedharanunni , Minu Singh , Emine Rahman , M.V. Archana , Amita Trehan

引用次数: 0

Marked microcytosis and increased transferrin saturation: Think about variants in SLC11A2 (DMT1) 明显的小红细胞症和转铁蛋白饱和度升高：考虑 SLC11A2（DMT1）的变异。

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2024-11-02 DOI: 10.1016/j.bcmd.2024.102898

Alexandre Raynor , Katell Peoc'h , Camille Boi , Hana Manceau , Serge Pissard , Karim Diallo , Caroline Kannengiesser , Pierre Rohrlich

引用次数: 0

Identification of Nfel1a and Nfel3 as novel regulators for zebrafish thrombopoiesis 鉴定 Nfel1a 和 Nfel3 作为斑马鱼血栓形成的新型调节器

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2024-10-10 DOI: 10.1016/j.bcmd.2024.102897

Weam Fallatah, Sanchi Dhinoja, Ayah Al Qaryoute, Jabila Mary, Vallerie Cheng, Pudur Jagadeeswaran

{"title":"Identification of Nfel1a and Nfel3 as novel regulators for zebrafish thrombopoiesis","authors":"Weam Fallatah, Sanchi Dhinoja, Ayah Al Qaryoute, Jabila Mary, Vallerie Cheng, Pudur Jagadeeswaran","doi":"10.1016/j.bcmd.2024.102897","DOIUrl":"10.1016/j.bcmd.2024.102897","url":null,"abstract":"<div><div>In mammalian hematopoiesis, megakaryocytes mature and become polyploid in the bone marrow before releasing platelets into circulation. In contrast, fish produce thrombocytes in kidney marrow, where young thrombocytes undergo maturation in circulation, akin to platelets. Despite morphological differences, our single-cell sequencing revealed significant gene expression similarities between fish thrombocytes and mammalian megakaryocytes, including Nfe2, which is crucial in platelet production. In addition to <em>nfe2</em> expression, we found four <em>nfe2-</em>related genes, <em>nfe2I1a, nfe2I1b, nfe2I2a,</em> and <em>nfe2I3,</em> were expressed in mature thrombocytes. However, only <em>nfe2, nfe2l2a,</em> and <em>nfe2l3</em> are expressed in young thrombocytes. Thus, we hypothesized that Nfe2-related factors may also be involved in thrombocyte production. To address this, we knocked down the four novel <em>nfe2-</em>related genes by the piggyback method and found both young and mature thrombocytes reduced when <em>nfe2, nfe2l1a,</em> and <em>nfe2l3</em> were knocked down. They also exhibited greater gill bleeding and prolonged time to occlusion (TTO) compared to controls. In summary, our study shows Nfe2I1a and Nfe2l3 as novel transcription factors that are positive regulators influencing adult zebrafish thrombopoiesis.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102897"},"PeriodicalIF":2.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442845","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}

引用次数: 0

Hemophagocytic lymphohistiocytosis associated with immune checkpoint inhibitor use: A review of the current knowledge and future directions 与使用免疫检查点抑制剂相关的嗜血细胞淋巴组织细胞增多症：回顾当前知识和未来方向。

IF 2.1 4区医学

Blood Cells Molecules and Diseases Pub Date : 2024-09-30 DOI: 10.1016/j.bcmd.2024.102896

Charlotte S. Walmsley , Zachary Schoepflin , Charlotte De Brabandt , Deepa Rangachari , Shana Berwick , Rushad Patell

{"title":"Hemophagocytic lymphohistiocytosis associated with immune checkpoint inhibitor use: A review of the current knowledge and future directions","authors":"Charlotte S. Walmsley , Zachary Schoepflin , Charlotte De Brabandt , Deepa Rangachari , Shana Berwick , Rushad Patell","doi":"10.1016/j.bcmd.2024.102896","DOIUrl":"10.1016/j.bcmd.2024.102896","url":null,"abstract":"<div><div>Hemophagocytic lymphohistiocytosis (HLH) is a severe and often lethal inflammatory syndrome characterized by excessive immune activation leading to fever, cytopenias, and multiorgan involvement. Immune checkpoint inhibitors (ICIs) are central to many contemporary cancer regimens, but their use is associated with immune-related adverse events. Here, we report a case of ICI-induced HLH successfully treated with single agent dexamethasone and provide a scoping review of the literature for cases of ICI-induced HLH with a focus on treatment strategies and outcomes. Using the Medline database, we searched for cases of ICI-associated HLH, with a total of 51 cases reported between 2017 and 2023. Our results underscore the severe nature of this disease, with a 13.7 % mortality rate across 51 case reports. Treatment strategies for ICI-induced HLH were variable: steroids alone (56.9 %), steroids with etoposide (17.6 %), steroids with tociluzumab (11.8 %), among other combinations. Our literature review indicates that steroids alone may be sufficient treatment in some cases of ICI-HLH, with comparable mortality with steroids alone (<em>n</em> = 29) (13.8 %) to that of cases treated with both steroids and immunomodulators (<em>n</em> = 15, 13.3 %). Moreover, all patients treated with steroids and tocilizumab survived (<em>n</em> = 6), suggesting that tocilizumab may be a reasonable next line of therapy when steroid monotherapy proves inadequate. We propose an outline for investigation and treatment of this rare complication of ICI use. Finally, we discuss possible future approaches to develop evidence-based strategies for the diagnosis and management of ICI-induced HLH including the importance of integrating the role of patient community involvement.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102896"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375048","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}

引用次数: 0