Pathology, research and practice最新文献_第9页

Unraveling extracellular vesicle DNA: Biogenesis, functions, and clinical implications 揭示细胞外囊泡DNA：生物发生、功能和临床意义

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155937

Mehraneh Nouri , Fateme Nasiri , Samaneh Sharif , Mohammad Reza Abbaszadegan

{"title":"Unraveling extracellular vesicle DNA: Biogenesis, functions, and clinical implications","authors":"Mehraneh Nouri , Fateme Nasiri , Samaneh Sharif , Mohammad Reza Abbaszadegan","doi":"10.1016/j.prp.2025.155937","DOIUrl":"10.1016/j.prp.2025.155937","url":null,"abstract":"<div><div>Extracellular Vesicles (EVs) have emerged as essential carriers of molecular biomarkers and mediators of intercellular communication. While previous studies have predominantly focused on EV proteins, lipids, and RNA, the role of EV-derived DNA (EV-DNA) remains relatively unexplored. Understanding EV-DNA is crucial, given its association with nearly all EV populations. This review aims to comprehensively summarize existing EV-DNA research, emphasizing its functional significance and potential as a disease biomarker. By bridging the gap in our understanding, we shed light on the origins, structure, localization, and distribution of EV-DNA. We analyze a wide range of studies, investigating EV-DNA across various pathological conditions. Our review encompasses experimental methods, theoretical approaches, and clinical observations, providing a holistic view of EV-DNA research. We discuss the biogenesis mechanisms of different EV subtypes, the available isolation methods for these subtypes, and consider their origins and variability under different conditions. EV-DNA exhibits remarkable stability and reflects genomic alterations, making it a promising candidate for liquid biopsy applications. From cancer diagnostics to treatment monitoring, EV-DNA holds significant potential. The findings underscore the importance of EV-DNA as an innovative biomarker. As research continues, EV-DNA may revolutionize disease detection, prognosis, and therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155937"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785391","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

CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy 肺癌中的CAR - T细胞：靶向肿瘤相关抗原，彻底改变免疫治疗

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155947

Sattam Khulaif Alenezi

{"title":"CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy","authors":"Sattam Khulaif Alenezi","doi":"10.1016/j.prp.2025.155947","DOIUrl":"10.1016/j.prp.2025.155947","url":null,"abstract":"<div><div>Tumor-targeted T cells engineered for targeting and killing tumor cells have revolutionized cancer treatment, specifically in hematologic malignancies, through chimeric antigen receptor (CAR) T cell therapy. However, the migration of this success to lung cancer is challenging due to the tumor microenvironment (TME), antigen heterogeneity, and limitations of T cell infiltration. This review aims to evaluate current strategies addressing these barriers, focusing on the optimization of tumor-associated antigen (TAA) targeting, such as epidermal growth factor receptor (EGFR), mucin-1 (MUC1), and mesothelin (MSLN), which are frequently overexpressed in lung cancer and offer promising targets for CAR T-cell therapy. In this review, we discuss recent progress in CAR T cell engineering, applying enhanced costimulatory molecules, cytokine-secreting CAR T cells, and engineered modifications to improve T cell resilience in immunosuppressive environments. Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155947"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748670","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

Toll-like receptors in kidney ischemia-reperfusion injury: Modulating macrophage responses for therapeutic insights 肾缺血再灌注损伤中的toll样受体：调节巨噬细胞反应的治疗见解

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155940

H. Malathi , Gaurav Khandelwal , S. Gayathri , Samir Sahoo , Swati Sharma

{"title":"Toll-like receptors in kidney ischemia-reperfusion injury: Modulating macrophage responses for therapeutic insights","authors":"H. Malathi , Gaurav Khandelwal , S. Gayathri , Samir Sahoo , Swati Sharma","doi":"10.1016/j.prp.2025.155940","DOIUrl":"10.1016/j.prp.2025.155940","url":null,"abstract":"<div><div>Kidney ischemia-reperfusion (I/R) injury is an acute clinical condition associated with inflammation and tissue damage during and after ischemia and reperfusion periods. In I/R injury, macrophages contribute to injury, and a family of proteins called toll-like receptors seem to have an immune modulatory role. When activated, TLRs initiate a series of signaling pathways, including MyD88 and TRIF. These pathways regulate the activation of tissue macrophages into either ‘classically activated’ M1 or ‘alternatively activated’ M2 phenotypes. Indeed, the relative abundance of these macrophage phenotypes defines the tissue injury level, which consequently requires reparative processes. The initial effector pro-inflammatory M1 macrophages aggravate tissue injury. Conversely, tissue reparative and anti-inflammatory M2 macrophages promote tissue repair and resolution—increased TLR signalling results in increased inflammation, prolonged healing and even renal failure. New evidence indicates that the change of macrophage responses through pharmacological targeting of the TLR pathways that regulate inflammation and tissue repair may have therapeutic implications. Some experimental treatment methods, in which early phases have been elaborated through experimental animal models, are TLR antagonists, small molecule inhibitors and nanotechnology-based delivery systems for Antisense oligonucleotide. Nevertheless, because the pathways regulated by TLRs and the subsets of macrophages are so countless and entangled, more extensive study is needed to provide more targeted actions. These findings shed light on the role and regulation of TLRs in macrophages during kidney I/R injury and investigate potential treatments with the potential to enhance care in this highly damaging condition.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155940"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748673","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

Recent developments in cuproptosis of glioblastoma 胶质母细胞瘤铜增生的最新进展

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155939

Yajia Chen , Jingxian Zhang , Hongwu Xu

{"title":"Recent developments in cuproptosis of glioblastoma","authors":"Yajia Chen , Jingxian Zhang , Hongwu Xu","doi":"10.1016/j.prp.2025.155939","DOIUrl":"10.1016/j.prp.2025.155939","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most malignant tumor within the central nervous system, attributed to its high-grade malignancy, propensity for recurrence, refractoriness to conventional therapeutic modalities, and the suboptimal efficacy of current targeted therapies. Hence, there is an urgent need to identify more efficacious molecular targets for the therapeutic intervention of GBM. The regulated cell death (RCD) has specific signaling factors and signaling pathways. Hence, targeting RCD is considered to be one of the effective targeted therapies for GBM. At present, cuproptosis is a novel form of RCD, characterized by a distinct molecular mechanism that differentiates it from apoptosis, pyroptosis, necroptosis, and ferroptosis. It is characterized by its principal mechanisms, which include copper dependency, the accumulation of acylated proteins, and the reduction of Fe-S cluster-containing proteins. These processes collectively induce proteotoxic stress, culminating in cell death. In previous studies, copper-ionized formulations have demonstrated cytotoxic effects on gliomas. Thus, the key factors of cuproptosis may be able to serve as a new target for GBM treatment. This review delves into several pivotal aspects, including the discovery of cuproptosis, the impact of copper homeostasis on tumorigenesis, the role of cuproptosis in GBM, and its potential as a therapeutic target in molecular targeted therapy for GBM. Hence, this article could reveal novel strategies for GBM treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155939"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735273","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

Renal expression and clinical significance of Bach1-related oxidative stress indicators in patients with chronic glomerulonephritis 慢性肾小球肾炎患者肾中bach1相关氧化应激指标的表达及临床意义

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155935

Hui Zhang , Xiao-lin Li , Jing-yao Lu , Qi Ke , Jun Li , Yuan Du , Ya-fen Yu

{"title":"Renal expression and clinical significance of Bach1-related oxidative stress indicators in patients with chronic glomerulonephritis","authors":"Hui Zhang , Xiao-lin Li , Jing-yao Lu , Qi Ke , Jun Li , Yuan Du , Ya-fen Yu","doi":"10.1016/j.prp.2025.155935","DOIUrl":"10.1016/j.prp.2025.155935","url":null,"abstract":"<div><div>Chronic glomerulonephritis (CGN) and diabetic kidney disease are the primary causes of chronic kidney disease in China. Oxidative stress participates in both the glomerular damage and tubular injury of glomerular diseases. In this study, we evaluated the renal expression and clinical significance of Bach1-associated oxidative stress markers in IgA nephropathy (IgAN), membranous nephropathy (MN) and diabetic nephropathy (DN) using immunohistochemical staining. Our study demonstrated that there was significantly increased expression of Bach1 in the renal tubular injury of all the patients with chronic glomerulonephritis yet with faint expression in glomerular endothelial cells. However, the expression levels of SLC25A39 and Grx2 were significantly decreased in the renal tubular lesions. The renal expression levels of 4-HNE were significantly elevated in the renal tubular injury of all the patients. While the expression levels of MDA were significantly higher in the renal lesions of patients with IgAN and DN compared to the patients with MN. The semi-quantitative scores of renal Bach1 and 4-HNE expression were positively correlated with the renal injury indicators. Whereas the semi-quantitative scores of renal SLC25A39 and Grx2 expression demonstrated a negative correlation with the renal injury indicators. Bach1-associated oxidative stress indicators may be the promising pathologic biomarkers of oxidative stress injury in the tubular injury of patients with chronic glomerulonephritis, which proposed potential therapeutic target.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155935"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769206","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

Fucoxanthin alleviates secondary brain injury in mice following intracerebral hemorrhage via PI3K-mediated inhibition of NF-κB signaling pathway 岩藻黄素通过pi3k介导的抑制NF-κB信号通路减轻小鼠脑出血后继发性脑损伤

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155933

WeiBing Liu, WenHua Xu

{"title":"Fucoxanthin alleviates secondary brain injury in mice following intracerebral hemorrhage via PI3K-mediated inhibition of NF-κB signaling pathway","authors":"WeiBing Liu, WenHua Xu","doi":"10.1016/j.prp.2025.155933","DOIUrl":"10.1016/j.prp.2025.155933","url":null,"abstract":"<div><h3>Background</h3><div>ICH is an acute clinical cerebrovascular disease without effective treatments. This study was designed to investigate the therapeutic value of fucoxanthin in ICH treatment.</div></div><div><h3>Methods</h3><div>Animal ICH models were established by collagenase IV injection. ICH mice were given intraperitoneal injection of fucoxanthin (100mg/kg). Neurological deficits, brain edema, blood-brain barrier (BBB) integrity, and histological impairment were assessed. Nissl staining and TUNEL staining were performed to detect neuronal cell loss and apoptosis. The levels of tight junction proteins, apoptosis-related proteins, Iba-1, and pathway-related proteins were measured by immunofluorescence staining, western blotting, and ELISA.</div></div><div><h3>Results</h3><div>Fucoxanthin administration attenuated neurological deficits and brain injuries following ICH. Additionally, fucoxanthin alleviated neuronal apoptosis caused by ICH. Moreover, fucoxanthin inhibited microglia-mediated inflammation and M1 polarization in ICH models. Mechanistically, fucoxanthin inactivated the NF-κB pathway and triggered the activation of PI3K/Akt signaling after ICH, and LY294002 (a PI3K inhibitor) compromised the protective effect of fucoxanthin.</div></div><div><h3>Conclusion</h3><div>Fucoxanthin alleviates ICH-induced neurological deficits and brain injuries by suppressing the PI3K/Akt-mediated NF-κB pathway to inhibit M1 polarization and attenuate neuroinflammation, neuronal apoptosis, BBB dysfunction, and brain edema.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155933"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834579","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

Exosomes in melanoma: Future potential for clinical theranostics 黑色素瘤中的外泌体：临床治疗的未来潜力

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155950

Asmit Das , Swarup Sonar , Rajib Dhar , Vetriselvan Subramaniyan

{"title":"Exosomes in melanoma: Future potential for clinical theranostics","authors":"Asmit Das , Swarup Sonar , Rajib Dhar , Vetriselvan Subramaniyan","doi":"10.1016/j.prp.2025.155950","DOIUrl":"10.1016/j.prp.2025.155950","url":null,"abstract":"<div><div>Melanoma, an aggressive form of skin cancer, presents significant therapeutic challenges due to its resistance to conventional treatments and propensity for metastasis. Exosomes, nanoscale vesicles secreted by a wide variety of cells, have emerged as promising tools for developing novel melanoma therapies. Exosome-based therapeutic approaches offer several advantages, including inherent biocompatibility, low immunogenicity, and the ability to cross biological barriers. This review explores the therapeutic potential of exosomes in melanoma treatment, focusing on their multifaceted roles in modulating tumor cell behavior, enhancing anti-tumor immune responses, and serving as targeted drug delivery vehicles. We discuss various strategies employed to engineer exosomes for enhanced therapeutic efficacy, including loading them with chemotherapeutic agents, small interfering RNAs (siRNAs), microRNAs (miRNAs), and immunomodulatory molecules. Additionally, we highlight the potential of exosomes derived from diverse sources to enhance anti-cancer effects. Furthermore, we address the challenges and future directions in translating exosome-based therapies from bench to bedside, emphasizing the need for standardized isolation and manufacturing protocols, as well as rigorous preclinical and clinical evaluations to unlock the full therapeutic potential of exosomes in the fight against melanoma.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155950"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759573","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

Multiomics evaluation and machine learning optimize molecular classification, prediction of prognosis and immunotherapy response for ovarian cancer 多组学评估和机器学习优化卵巢癌的分子分类、预测预后和免疫治疗反应

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155925

Fang Ren , Xiaoao Pang , Ning Liu, Liancheng Zhu

{"title":"Multiomics evaluation and machine learning optimize molecular classification, prediction of prognosis and immunotherapy response for ovarian cancer","authors":"Fang Ren , Xiaoao Pang , Ning Liu, Liancheng Zhu","doi":"10.1016/j.prp.2025.155925","DOIUrl":"10.1016/j.prp.2025.155925","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC), owing to its substantial heterogeneity and high invasiveness, has historically been devoid of precise, individualized treatment options. This study aimed to establish integrated consensus subtypes of OC using different multiomics integration methodologies.</div></div><div><h3>Methods</h3><div>We integrated five distinct multiomics datasets from multicentric cohorts to identify high-resolution molecular subgroups using a combination of 10 and 101 clustering and machine learning algorithms, respectively, to develop a robust consensus multiomics-related machine learning signature (CMMS).</div></div><div><h3>Results</h3><div>Two cancer subtypes with prognostic significance were identified using multiomics clustering analysis. 10 essential genes were identified in the CMMS. Patients in the high CMMS group exhibited a poorer prognosis, with a “cold tumor” phenotype and an immunosuppressive state with reduced immune cell infiltration. In contrast, patients in the low CMMS group exhibited a more favorable prognosis, with immune activation and a “hot tumor\" phenotype characterized by increased tumor mutation burden, tumor neoantigen burden, PD-L1 expression, and enriched M1 macrophages. Eight independent immunotherapy datasets were validated to further corroborate our findings regarding patients in the low CMMS group who responded better to immunotherapy.</div></div><div><h3>Conclusions</h3><div>CMMS detection has significant utility in the prognosis of patients at an early stage and identification of potential candidates for immunotherapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155925"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748144","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

A novel variation in the LMX1B gene with nail-patella syndrome 指甲-髌骨综合征中LMX1B基因的新变异

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155936

Lu Zhang , Jilong Xiong , Hiu-Ming Li , Xia Li , Xuewen Yu , Yingying Liang , Huili Sun , ShuDong Yang , Mumin Shao

{"title":"A novel variation in the LMX1B gene with nail-patella syndrome","authors":"Lu Zhang , Jilong Xiong , Hiu-Ming Li , Xia Li , Xuewen Yu , Yingying Liang , Huili Sun , ShuDong Yang , Mumin Shao","doi":"10.1016/j.prp.2025.155936","DOIUrl":"10.1016/j.prp.2025.155936","url":null,"abstract":"<div><div>Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disorder characterized by developmental defects in dorsal limb structures, kidneys, and eyes. The incidence of NPS is attributed to variations in the <em>LMX1B</em> gene. In this report, we present a novel <em>LMX1B</em> variation identified in a Chinese family affected by NPS. The proband, a 15-year-old male, exhibited a history of proteinuria and microscopic hematuria accompanied by renal dysfunction, nail dysplasia, bilateral patellar dysplasia, bilateral shoulder and elbow joint dysplasia and iliac horns. Histological examination revealed mild glomerular lesions. Under electron microscopy, irregular thickening of the glomerular basement membrane was observed, characterized by an appearance resembling occasional electron lucent areas (\"moth-eaten\" appearance) and the presence of disorganized collagen fiber bundles. Pathological findings were consistent with NPS. Genetic analysis identified a novel heterozygous variant, c.791 A>C, p.(Gln264Pro), in the patient, his father and younger brother. This new variant has been annotated as potentially pathogenic according to the recommendation of the American Society for Medical Genetics and Genomics. This represents the first report of a novel variation in the <em>LMX1B</em> gene. These findings expand the spectrum of variations associated with <em>LMX1B</em> in NPS.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155936"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748172","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

GATA1 insufficiencies in dysmegakaryopoiesis of myelodysplastic syndromes/neoplasms 骨髓增生异常综合征/肿瘤的巨核发育异常中的GATA1缺陷

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155930

Fuhui Li , Yudi Zhang , Chengwen Li , Qi Sun , Jinqin Liu , Tiejun Qin , Zefeng Xu , Bing Li , Shiqiang Qu , Lijuan Pan , Qingyan Gao , Meng Jiao , Zhijian Xiao

{"title":"GATA1 insufficiencies in dysmegakaryopoiesis of myelodysplastic syndromes/neoplasms","authors":"Fuhui Li , Yudi Zhang , Chengwen Li , Qi Sun , Jinqin Liu , Tiejun Qin , Zefeng Xu , Bing Li , Shiqiang Qu , Lijuan Pan , Qingyan Gao , Meng Jiao , Zhijian Xiao","doi":"10.1016/j.prp.2025.155930","DOIUrl":"10.1016/j.prp.2025.155930","url":null,"abstract":"<div><div>GATA1 is one of critical transcription factors for megakaryopoiesis and platelet production. Our study aimed to explore the correlations between GATA1 expression and dysmegakaryopoiesis in myelodysplastic syndromes/neoplasm (MDS). We assessed GATA1 expression level of megakaryocytes by performing immunohistochemical staining on bone marrow biopsy sections from MDS patients. According to GATA1 expression level of megakaryocytes and positive megakaryocyte percentage, we assigned each patient a GATA1 score. Compared with <em>TP53</em>-wildtype patients, GATA1 scores significantly decreased in <em>TP53-</em>mutated patients (<em>P</em> < 0.001). Patients with abnormal karyotypes showed decreased GATA1 scores than those with normal karyotypes (<em>P</em> = 0.024). GATA1 expression levels were significantly downregulated in dysplastic megakaryocytes, especially micromegakaryocytes (<em>P</em> < 0.001). Furthermore, we explored the correlation between GATA1 expression levels and cytogenetic abnormalities of the same megakaryocyte using the morphology antibody chromosome (MAC) technique on fresh bone marrow smears. We found that GATA1-negative megakaryocytes had higher frequencies of cytogenetic abnormalities. Our results indicated that decreased GATA1 expression level of megakaryocytes was significantly associated with <em>TP53</em> mutations, abnormal karyotypes and dysmegakaryopoiesis in MDS, suggesting that downregulation of GATA1 expression levels of megakaryocytes plays a critical role in the pathogenesis of MDS.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155930"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748146","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