Experimental hematology最新文献

{"title":"The diagnostic and therapeutic potential of multiple myeloma–associated circular RNAs","authors":"Yue Zhao ,&nbsp;Shaokun Wang ,&nbsp;Shuang Fu,&nbsp;Xinxin Wang,&nbsp;Jihong Zhang,&nbsp;Fang Chen","doi":"10.1016/j.exphem.2024.104709","DOIUrl":"10.1016/j.exphem.2024.104709","url":null,"abstract":"<div><div>Circular RNA (circRNA) was first discovered in viruses in 1974; they are primarily formed through back splicing, where a downstream splice donor is joined to an upstream splice acceptor, resulting in a closed circRNA transcript. Under normal conditions, most circRNAs are stably expressed; however, in pathological conditions, circRNAs can play critical roles in the disease process of multiple myeloma (MM) through mechanisms such as competing endogenous RNAs (ceRNAs), regulation of transcription and splicing, affecting protein expression and localization, and even direct encoding of peptides. In recent years, there has been increasing interest in the role of circRNAs in MM and their regulatory functions during the disease process. Numerous studies have revealed that circRNAs are involved in the pathogenesis and prognosis of MM, aiding in the identification of reliable prognostic markers and potential therapeutic targets. Therefore, this review summarizes the structural characteristics of circRNAs, and their regulatory roles in MM, and introduces the latest advancements in understanding the novel functions of circRNAs in MM.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104709"},"PeriodicalIF":2.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930953","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":"FT-4202, a selective pyruvate kinase R activator for sickle cell disease","authors":"Anna Ericsson ,&nbsp;David J. Richard ,&nbsp;Erik Wilker ,&nbsp;David R. Lancia Jr. ,&nbsp;Shawn Fessler ,&nbsp;Paul Troccolo ,&nbsp;Xiaozhang Zheng ,&nbsp;Angela Toms ,&nbsp;Christopher Dinsmore ,&nbsp;Lili Yao ,&nbsp;Frans A. Kuypers ,&nbsp;Sandra Larkin ,&nbsp;Douglas Marcotte ,&nbsp;Keertik Fulzele ,&nbsp;Maria Ribadeneira ,&nbsp;Sylvie M. Guichard ,&nbsp;Gary Marshall","doi":"10.1016/j.exphem.2024.104673","DOIUrl":"10.1016/j.exphem.2024.104673","url":null,"abstract":"<div><div>Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin–oxygen (HbO₂) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased HbO₂ affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays. FT-4202, an allosteric PKR activator, stabilizes the tetrameric enzyme and increases PKR activity in human and mouse RBCs in vitro. Seven-day oral administration of FT-4202 in Berkeley SCD mice reduced 2,3-DPG, increased HbO₂ affinity, and reduced RBC sickling versus control. There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104673"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644307","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":"IFC Editorial Board","authors":"","doi":"10.1016/S0301-472X(24)00564-2","DOIUrl":"10.1016/S0301-472X(24)00564-2","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104700"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177746","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":"Structural diversity and function of the granulocyte colony-stimulating factor in medaka fish","authors":"Ayame Ogawa ,&nbsp;Shungo Konno ,&nbsp;Satoshi Ansai ,&nbsp;Kiyoshi Naruse ,&nbsp;Takashi Kato","doi":"10.1016/j.exphem.2024.104672","DOIUrl":"10.1016/j.exphem.2024.104672","url":null,"abstract":"<div><div>Diversity in the granulocyte repertoire, including neutrophils, basophils, and eosinophils, has been reported in vertebrate species. Medaka fish (<em>Oryzias latipes</em>) have only neutrophils; however, the storage pool of granulopoiesis tissues and the molecular mechanism of granulopoiesis in medaka fish have not been explored. Granulocyte colony-stimulating factor (G-CSF) is a cytokine responsible for neutrophil differentiation, survival, and proliferation. We performed in silico analysis to molecularly characterize the medaka G-CSF and G-CSF receptor (G-CSFR) genes. This study showed that medaka G-CSF differs considerably from human and mouse G-CSF in terms of the primary protein structure; however, the predicted tertiary structure was largely conserved. Analyses of lipopolysaccharide stimulation and G-CSF knockout and overexpression in medaka revealed that G-CSF mobilizes neutrophils into the peripheral blood. The analysis of G-CSF-deficient medaka revealed that G-CSF is involved in erythropoiesis. These findings represent an important first step toward understanding granulocyte hematopoiesis in nonmammalian species.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104672"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638408","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":"Platelet ultrastructural changes stored at room temperature versus cold storage observed by electron microscopy and structured illumination microscopy","authors":"Yang Sun ,&nbsp;Shunli Gu ,&nbsp;Yan Ma ,&nbsp;Aowei Song ,&nbsp;Lili Xing ,&nbsp;Jiameng Niu ,&nbsp;Ru Yang ,&nbsp;Xiaoyu Hu ,&nbsp;Wenhua Wang ,&nbsp;Ting Ma ,&nbsp;Fenfang Tian ,&nbsp;Liqin Wang ,&nbsp;Xinxin Xie ,&nbsp;Xiaofeng Huang ,&nbsp;Wen Yin ,&nbsp;Jiangcun Yang","doi":"10.1016/j.exphem.2024.104671","DOIUrl":"10.1016/j.exphem.2024.104671","url":null,"abstract":"<div><div>Our study seeks to provide a theoretical foundation for the clinical use of cold-stored platelets (CSPs) by interpreting ultrastructural images and quantitatively analyzing structural changes. CSPs, room temperature–stored platelets (RTPs), and delayed CSPs (delayed-CSPs) were continuously observed using scanning electron microscopy and transmission electron microscopy at eight time points. Super-resolution fluorescence microscopy was employed to observe changes in platelet microtubules and mitochondrial structure and function, whereas platelet counts, metabolism, and relevant functional indicators were measured concurrently. Quantitative statistical analysis of platelet size, morphology, canalicular systems, and five organelles was performed under electron microscopy. In CSPs stored for 1 day, the platelet shape changed from circular or elliptical to spherical, with size decreasing from 2.8 × 2.2 µm to 2.0 × 2.0 µm. CSPs exhibited wrinkling and reorganization of platelet microtubule proteins, with organelles aggregating toward the central region. CSPs stored for 14 days and delayed-CSPs for stored for 10 days exhibited numerous structurally intact and active cells. The percentage of structure-intact active cells was 92% in both groups, respectively. RTPs stored for 5 and 7 days showed minimal changes in size, a normal microtubule skeleton, and were primarily in a resting state. However, RTPs stored for 10 and 14 days displayed swelling, irregular disintegration of the microtubule skeleton, and the presence of membranous structures and vacuolated cells. The percentage of structure-intact active cells was only 45% and 7%, respectively. Our findings confirmed that the maximum storage time of platelets was 5–7 days for RTPs, within 10 days for delayed-CSPs, and 14 days for CSPs.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104671"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617211","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":"Microbiome and Hemato-immune Aging","authors":"Alban Johansson ,&nbsp;Nicole Pui-Yu Ho ,&nbsp;Hitoshi Takizawa","doi":"10.1016/j.exphem.2024.104685","DOIUrl":"10.1016/j.exphem.2024.104685","url":null,"abstract":"<div><div>The microbiome is a highly complex and diverse symbiotic component that undergoes dynamic changes with the organismal aging. Microbial perturbations, termed dysbiosis, exert strong influence on dysregulating the bone marrow niche and subsequently promoting the aging of hematopoietic and immune system. Accumulating studies have revealed the substantial impact of intestinal microbiome on the initiation and progression of age-related hematologic alteration and diseases, such as clonal hematopoiesis and blood cancers. Current therapeutic approaches to restore the altered microbiome diversity target specific pathobionts and are demonstrated to improve clinical outcomes of antihematologic malignancy treatments. In this review, we discuss the interplay between the microbiome and the hemato-immune system during aging process. We also shed light on the emerging therapeutic strategies to tackle the dysbiosis for amelioration of aging and disease progression.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104685"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708909","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":"Reconsidering the usual suspects in age-related hematologic disorders: is stem cell dysfunction a root cause of aging?","authors":"Foteini Fotopoulou ,&nbsp;Esther Rodríguez-Correa ,&nbsp;Charles Dussiau ,&nbsp;Michael D. Milsom","doi":"10.1016/j.exphem.2024.104698","DOIUrl":"10.1016/j.exphem.2024.104698","url":null,"abstract":"<div><div>Aging exerts a profound impact on the hematopoietic system, leading to increased susceptibility to infections, autoimmune diseases, chronic inflammation, anemia, thrombotic events, and hematologic malignancies. Within the field of experimental hematology, the functional decline of hematopoietic stem cells (HSCs) is often regarded as a primary driver of age-related hematologic conditions. However, aging is clearly a complex multifaceted process involving not only HSCs but also mature blood cells and their interactions with other tissues. This review reappraises an HSC-centric view of hematopoietic aging by exploring how the entire hematopoietic hierarchy, from stem cells to mature cells, contributes to age-related disorders. It highlights the decline of both innate and adaptive immunity, leading to increased susceptibility to infections and cancer, and the rise of autoimmunity as peripheral immune cells undergo aging-induced changes. It explores the concept of “inflammaging,” where persistent, low-grade inflammation driven by old immune cells creates a cycle of tissue damage and disease. Additionally, this review delves into the roles of inflammation and homeostatic regulation in age-related conditions such as thrombotic events and anemia, arguing that these issues arise from broader dysfunctions rather than stemming from HSC functional attrition alone. In summary, this review highlights the importance of taking a holistic approach to studying hematopoietic aging and its related pathologies. By looking beyond just stem cells and considering the full spectrum of age-associated changes, one can better capture the complexity of aging and attempt to develop preventative or rejuvenation strategies that target multiple facets of this process.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104698"},"PeriodicalIF":2.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893333","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":"The inhibitory receptor PVRIG is dominantly expressed in the bone marrow of patients with multiple myeloma and its blockade enhances T-cell engager's immune activation","authors":"Masha Frenkel ,&nbsp;Zoya Alteber ,&nbsp;Ning Xu ,&nbsp;Mingjie Li ,&nbsp;Haiming Chen ,&nbsp;Deborah Hayoun ,&nbsp;Roy Zvi Granit ,&nbsp;Gady Cojocaru ,&nbsp;James Berenson ,&nbsp;Eran Ophir","doi":"10.1016/j.exphem.2024.104696","DOIUrl":"10.1016/j.exphem.2024.104696","url":null,"abstract":"<div><div>Therapeutic advances in treating patients with multiple myeloma (MM), including novel immunotherapies, have improved the disease control, but it remains incurable. Although traditional immune check point inhibitors have shown limited clinical benefit, targeting alternative immune-inhibitory pathways may offer a novel way to address relapsed disease. Blockade of the immune regulator TIGIT was shown to enhance antitumor immunity in preclinical MM models. Beyond TIGIT, the DNAM-1 axis includes the novel inhibitory receptor PVR related immunoglobulin (PVRIG). In this study we evaluated the expression of DNAM-1 axis receptors and the function of PVRIG in bone marrow of individuals with MM, specifically highlighting PVRIG blockade as a potential therapeutic opportunity in combination with bispecific T-cell engager (BiTE).</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104696"},"PeriodicalIF":2.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853596","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":"Understanding Human Oncogene Function and Cooperativity in Myeloid Malignancy Using iPSCs","authors":"Martina Sarchi ,&nbsp;Sergei Doulatov","doi":"10.1016/j.exphem.2024.104697","DOIUrl":"10.1016/j.exphem.2024.104697","url":null,"abstract":"<div><div>Myeloid malignancies are a spectrum of clonal disorders driven by genetic alterations that cooperatively confer aberrant self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs). Induced pluripotent stem cells (iPSCs) can be differentiated into HSPCs and have been widely explored for modeling hematologic disorders and cell therapies. More recently, iPSC models have been applied to study the origins and pathophysiology of myeloid malignancies, motivated by the appreciation for the differences in human oncogene function and the need for genetically defined models that recapitulate leukemia development. In this review, we will provide a broad overview of the rationale, the challenges, practical aspects, history, and recent advances of iPSC models for modeling myeloid neoplasms. We will focus on the insights into the previously unknown aspects of human oncogene function and cooperativity gained through the use of these models. It is now safe to say that iPSC models are a mainstay of leukemia modeling “toolbox” alongside primary human cells from normal and patient sources.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104697"},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824060","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":"RNA methylation: where to from here for hematologic malignancies?","authors":"Andrew Adel Guirguis","doi":"10.1016/j.exphem.2024.104694","DOIUrl":"10.1016/j.exphem.2024.104694","url":null,"abstract":"<div><div>RNA methylation and the machinery that regulates or “reads” its expression has recently been implicated in the pathogenesis of acute myeloid leukemia (AML) and other hematologic malignancies. Modulation of these epigenetic marks has started to become a reality as several companies around the world seek to leverage this knowledge therapeutically in the clinic. Although the bases of observed activity in AML have been described by numerous groups, the exact context in which these therapies will ultimately be used remains to be properly determined. While context is likely to be of great importance here, a more “global” mechanism of action might allow for more widespread applicability to multiple disease subtypes. In other areas such as the myelodysplastic and other preleukemic syndromes, data remain sparse. Ongoing work is needed to determine whether therapeutic modulation of RNA modifications is a viable and biologically plausible approach in these cases. Regardless of the outcomes, this is an exciting era for “epitranscriptomics” as we navigate a pathway forward. Here, I describe the current knowledge around RNA methylation and hematologic malignancies at the end of 2024 including some of the relevant questions that are yet to be answered.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104694"},"PeriodicalIF":2.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794364","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}