Clinical and Experimental Medicine最新文献

{"title":"Targeting sphingolipid metabolism in chronic lymphocytic leukemia.","authors":"Flora Nguyen Van Long, Trang Le, Patrick Caron, Délya Valcourt-Gendron, Roxanne Sergerie, Isabelle Laverdière, Katrina Vanura, Chantal Guillemette","doi":"10.1007/s10238-024-01440-x","DOIUrl":"10.1007/s10238-024-01440-x","url":null,"abstract":"<p><p>Elevated levels of circulating C16:0 glucosylceramides (GluCer) and increased mRNA expression of UDP-glucose ceramide glycosyltransferase (UGCG), the enzyme responsible for converting ceramides (Cer) to GluCer, represent unfavorable prognostic markers in chronic lymphocytic leukemia (CLL) patients. To evaluate the therapeutic potential of inhibiting GluCer synthesis, we genetically repressed the UGCG pathway using in vitro models of leukemic B cells, in addition to UGCG pharmacological inhibition with approved drugs such as eliglustat and ibiglustat, both individually and in combination with ibrutinib, assessed in cell models and primary CLL patient cells. Cell viability, apoptosis, and proliferation were evaluated in vitro, and survival and apoptosis were examined ex vivo. UGCG inhibition efficacy was confirmed by quantifying intracellular sphingolipid levels through targeted lipidomics using mass spectrometry. Other inhibitors of sphingolipid biosynthesis pathways were similarly assessed. Blocking UGCG significantly decreased cell viability and proliferation, highlighting the oncogenic role of UGCG in CLL. The efficient inhibition of UGCG was confirmed by a significant reduction in GluCer intracellular levels. The combination of UGCG inhibitors with ibrutinib demonstrated synergistic effect. Inhibitors that target alternative pathways within sphingolipid metabolism, like sphingosine kinases inhibitor SKI-II, also demonstrated promising therapeutic effects both alone and when used in combination with ibrutinib, reinforcing the oncogenic impact of sphingolipids in CLL cells. Targeting sphingolipid metabolism, especially the UGCG pathway, represents a promising therapeutic strategy and as a combination therapy for potential treatment of CLL patients, warranting further investigation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"174"},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792118","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":"Characterization of cells and mediators associated with pruritus in primary cutaneous T-cell lymphomas","authors":"Man Hu, Jörg Scheffel, Stefan Frischbutter, Carolin Steinert, Ulrich Reidel, Max Spindler, Katarzyna Przybyłowicz, Marlena Hawro, Marcus Maurer, Martin Metz, Tomasz Hawro","doi":"10.1007/s10238-024-01407-y","DOIUrl":"https://doi.org/10.1007/s10238-024-01407-y","url":null,"abstract":"<p>Patients with primary cutaneous T-cell lymphoma (CTCL) often experience severe and difficult-to-treat pruritus that negatively affects their quality of life (QoL). However, the mechanisms of pruritus in CTCL, including mycosis fungoides (MF), remain largely unknown, and detailed characteristics of CTCL-associated pruritus is not fully elucidated. To characterize pruritus in CTCL, cutaneous B-cell lymphoma (CBCL), and large plaque parapsoriasis (LPP), and to identify potential itch mediators involved in the pathogenesis of pruritus in CTCL patients. Clinical data and blood samples were collected from 129 healthy subjects and 142 patients. Itch intensity, QoL impairment, psychological distress, and sleep quality were assessed using validated questionnaires and instruments. Blood levels of BDNF, CCL24, GRP, IL-31, IL-33, sST2, substance P, TSLP, tryptase and total IgE were measured using ELISA or ImmunoCAP. Pruritus was prevalent in CTCL, LPP and CBCL patients, with higher prevalence and severity observed in CTCL. In CTCL, pruritus correlated with significant impairment in QoL, sleep, psychological distress. Compared to healthy controls, elevated levels of IL-31, IL-33, substance P, total IgE, tryptase, and TSLP were found in MF patients. A comparison of MF patients with and without pruritus revealed higher levels of IL-31, substance P, GRP, and CCL24 in the former. Itch intensity positively correlated with IL-31, GRP, CCL24, and tryptase levels. Pruritus significantly burdens CTCL patients, necessitating appropriate therapeutic management. Our findings suggest that various non-histaminergic mediators such as tryptase and IL-31 could be explored as novel therapeutic targets for managing pruritus in MF patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"12 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141776822","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":"High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis","authors":"Shimon Izhakian, May Igawa, Liora Chen Zion, Ori Mekiten, Lev Freidkin, Dror Rosengarten, Moshe Heching, Mordechai Reuven Kramer","doi":"10.1007/s10238-024-01447-4","DOIUrl":"https://doi.org/10.1007/s10238-024-01447-4","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14−4.42, <i>P</i> = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07−2.25, <i>P</i> = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"22 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141776823","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 tissue IgG4 levels in steroid therapy in patients with idiopathic granulomatous mastitis.","authors":"Celil Seyidli, Yunushan Furkan Aydoğdu, Çağrı Büyükkasap, Ramazan Kozan, Mahir Nasirov, Kürşat Dikmen, Güldal Esendağli Yilmaz, Murat Akin","doi":"10.1007/s10238-024-01444-7","DOIUrl":"10.1007/s10238-024-01444-7","url":null,"abstract":"<p><p>Idiopathic granulomatous mastitis (IGM) is a benign, chronic inflammatory lesion of the breast. Immunoglobulin G4 (IgG4) associated disease is rare in the breast. In our study, we aimed to evaluate the efficacy of steroid treatment on IgG4 levels in tissue in patients diagnosed with IGM. Between 2008 and 2017, 55 patients diagnosed with IGM in our clinic were included in the study. Demographic, clinical, microbiologic and histopathologic characteristics, treatment modality and recovery time were evaluated retrospectively. Patients were divided into 3 groups according to tissue IgG4 levels: negative (Group I), infrequently and slightly positive (Group II), and highly positive (Group III). Group I patients had a complete response rate of 77.8%. In the rest of the patients (22.2%), insufficient response was detected from the beginning of the treatment. In Group II, the response rate was 91.3% and the permanent success rate after treatment was 87.0%. Although group III patients had a complete response at the beginning (95.65%), they relapsed in a short period of time (26.1%) after discontinuation of steroid treatment. At least one steroid-related side effect was observed in 47 (85.8%) patients in all groups. There is no consensus on the dose and duration of immunosuppressive treatment in IGM. In this study, responses to steroid treatment according to IgG4 concentration in pathologic breast tissue and recurrences after the end of treatment were determined. We think that high IgG4 concentration in the tissue is associated with recurrence and other immunosuppressive drugs should be added as maintenance after steroid treatment.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"173"},"PeriodicalIF":3.2,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787374","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":"Single-cell sequencing reveals novel proliferative cell type: a key player in renal cell carcinoma prognosis and therapeutic response.","authors":"Bicheng Ye, Hongsheng Ji, Meng Zhu, Anbang Wang, Jingsong Tang, Yong Liang, Qing Zhang","doi":"10.1007/s10238-024-01424-x","DOIUrl":"10.1007/s10238-024-01424-x","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is characterized by a variety of subtypes, each defined by unique genetic and morphological features. This study utilizes single-cell RNA sequencing to explore the molecular heterogeneity of RCC. A highly proliferative cell subset, termed as \"Prol,\" was discovered within RCC tumors, and its increased presence was linked to poorer patient outcomes. An artificial intelligence network, encompassing traditional regression, machine learning, and deep learning algorithms, was employed to develop a Prol signature capable of predicting prognosis. The signature demonstrated superior performance in predicting RCC prognosis compared to other signatures and exhibited pan-cancer prognostic capabilities. RCC patients with high Prol signature scores exhibited resistance to targeted therapies and immunotherapies. Furthermore, the key gene CEP55 from the Prol signature was validated by both proteinomics and quantitative real time polymerase chain reaction. Our findings may provide new insights into the molecular and cellular mechanisms of RCC and facilitate the development of novel biomarkers and therapeutic targets.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"167"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757497","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 application of organoids in cancers associated with pathogenic infections.","authors":"Yuyu Zhang, Tao Liu, Wenting He","doi":"10.1007/s10238-024-01435-8","DOIUrl":"10.1007/s10238-024-01435-8","url":null,"abstract":"<p><p>Cancers associated with pathogen infections are gradually becoming important threats to human health globally, and it is of great significance to study the mechanisms of pathogen carcinogenesis. Current mechanistic studies rely on animal and two-dimensional (2D) cell culture models, but traditional methods have been proven insufficient for the rapid modeling of diseases caused by new pathogens. Therefore, research focus has shifted to organoid models, which can replicate the structural and genetic characteristics of the target tissues or organs in vitro, providing new platforms for the study of pathogen-induced oncogenic mechanisms. This review summarizes the application of organoid technology in the studies of four pathogen-associated cancers: gastric cancer linked to Helicobacter pylori, liver cancer associated with hepatitis B virus or hepatitis C virus, colorectal cancer caused by Escherichia coli, and cervical cancer related to human papillomavirus. This review also proposes several limitations of organoid technology to optimize organoid models and advance the treatment of cancer associated with pathogen infections in the future.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"168"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757498","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":"Deciphering the prognostic role of endoplasmic reticulum stress in lung adenocarcinoma: integrating prognostic prediction and immunotherapy strategies.","authors":"Bing Wen, Pengpeng Zhang, Jiping Xie, Zhaokai Zhou, Ge Zhang, Lianmin Zhang, Zhenfa Zhang","doi":"10.1007/s10238-024-01439-4","DOIUrl":"10.1007/s10238-024-01439-4","url":null,"abstract":"<p><p>Endoplasmic reticulum stress (ERS) is a critical factor influencing lung adenocarcinoma (LUAD) progression and patient outcomes. In this study, we analyzed gene expression data from LUAD samples sourced from The Cancer Genomic Atlas and Gene Expression Omnibus databases. Utilizing advanced statistical methods including LASSO and Cox regression, we developed a ERS-associated signature (ERAS) based on ten ERS-related genes. This model stratified patients into high- and low-risk groups, with the high-risk group exhibiting decreased survival rates, elevated tumor mutational burden, and heightened chemotherapy sensitivity. Additionally, we observed lower immune and ESTIMATE scores in the high-ERAS group, indicating a potentially compromised immune response. Experimental validation through quantitative real-time polymerase chain reaction confirmed the utility of our model. Furthermore, we constructed a nomogram to predict 1-, 3-, and 5-year survival rates, providing clinicians with a valuable tool for personalized patient management. In conclusion, our study demonstrates the efficacy of the ERAS in identifying high-ERAS LUAD patients, offering promising implications for improved prognostication and treatment strategies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"169"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757496","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":"A systematic review and meta-analysis of the diagnostic accuracy of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in systemic lupus erythematosus.","authors":"Angelo Zinellu, Panagiotis Paliogiannis, Arduino A Mangoni","doi":"10.1007/s10238-024-01438-5","DOIUrl":"10.1007/s10238-024-01438-5","url":null,"abstract":"<p><p>The wide range of clinical and serological manifestations in systemic lupus erythematosus (SLE) and the lack of accepted diagnostic criteria warrant the identification of novel, more accurate biomarkers. Hematological indices derived from full blood cell counts, particularly the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have shown promise in SLE; however, a critical appraisal of their diagnostic accuracy is lacking. We sought to address this issue by conducting a systematic review and meta-analysis of the diagnostic accuracy of the NLR and PLR in SLE. The electronic databases PubMed, Scopus, and Web of Science were systematically searched from inception to 15 March 2024 for studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of SLE, disease severity, organ involvement (lupus nephritis, pericarditis, and pleural disease), and complications (infections). The risk of bias was assessed using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024531446). The NLR exhibited good accuracy for the diagnosis of SLE (eight studies; area under the curve, AUC = 0.81, 95% CI 0.78-0.85) and lupus nephritis (nine studies; AUC = 0.81, 95% CI 0.77-0.84), but not for severe disease (nine studies; AUC = 0.69, 95% CI 0.65-0.73) or infections (six studies; AUC = 0.73, 95% CI 0.69-0.77). The PLR exhibited good accuracy for the diagnosis of severe disease (six studies; AUC = 0.85, 95% CI 0.81-0.87). There were an insufficient number of studies to assess the accuracy of the PLR for the diagnosis of SLE, lupus nephritis, or infections. No study investigated the NLR and PLR in SLE patients with pericarditis or pleural disease. Therefore, the NLR and the PLR have a relatively high diagnostic accuracy for the presence of SLE and lupus nephritis (NLR) and severe disease (PLR). Further studies are warranted to determine whether the NLR and PLR, in combination with clinical evaluation and other serological biomarkers, can enhance the diagnosis and management of SLE.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"170"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757412","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":"Type XII collagen is elevated in serum from patients with solid tumors: a non-invasive biomarker of activated fibroblasts.","authors":"Marina Crespo-Bravo, Annika Hettich, Jeppe Thorlacius-Ussing, Thomas R Cox, Morten A Karsdal, Nicholas Willumsen","doi":"10.1007/s10238-024-01431-y","DOIUrl":"10.1007/s10238-024-01431-y","url":null,"abstract":"<p><p>Understanding the tumor microenvironment (TME) and extracellular matrix (ECM) is crucial in cancer research due to their impact on tumor progression. Collagens, major ECM components, regulate cell signaling and behavior. Of the 28 reported collagens, type XII collagen is known to be vital for ECM organization. Over-produced by cancer-associated fibroblasts (CAFs), its upregulation correlates with poor survival in various cancers. This study aimed to develop an ELISA for quantifying circulating type XII collagen as a cancer biomarker. A specific ELISA targeting the C-terminal of type XII collagen was developed and used to analyze serum samples from cancer patients (n = 203) and healthy controls (n = 33). Additionally, type XII collagen expression was assessed in CAFs and normal fibroblasts (NFs) from different tissues, both under TGF-β stimulated and non-stimulated conditions. The nordicPRO-C12 ELISA demonstrated robustness and specificity for type XII collagen. PRO-C12 levels were significantly elevated in patients with various cancers compared to healthy controls and effectively distinguished between cancer patients and controls. Findings were validated using gene expression data. Furthermore, Western blot analysis revealed increased type XII collagen expression in both CAFs and NFs upon TGF-β1 stimulation, suggesting a potential role of TGF-β1 in modulating the expression of type XII collagen in cancerous and normal tissue microenvironments. This study unveils a promising avenue for harnessing PRO-C12 as a non-invasive serum biomarker, enabling the quantification of type XII collagen fragments in cancer patients. Further investigations are warranted to explore the potential of PRO-C12 across different cancer types and disease stages, shedding light on its multifaceted role in cancer development.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"166"},"PeriodicalIF":3.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757499","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":"Value and limitations of targeted next-generation sequencing in idiopathic hypereosinophilia: an integrative diagnostic tool in challenging cases.","authors":"Daniele Cattaneo, Alfredo Marchetti, Cristina Bucelli, Nicole Galli, Marta Lionetti, Valentina Bellani, Umberto Gianelli, Francesco Passamonti, Niccolò Bolli, Alessandra Iurlo","doi":"10.1007/s10238-024-01441-w","DOIUrl":"10.1007/s10238-024-01441-w","url":null,"abstract":"<p><p>Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 28 consecutive patients admitted to our hospital between September 2011 and November 2021 for idiopathic hypereosinophilia (HE).Bone marrow (BM) morphology was evaluated in 22 patients: while in six subjects BM was unremarkable, in the remaining cases an increase in BM eosinophils was observed, together with a slight increase in BM fibrosis (MF-1) in 5/22 patients.A total of 4/28 patients had at least one genetic lesion by targeted NGS. In particular, the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33. Notably, JAK2V617F and TET2 mutations co-occurred, with the JAK2V617F-mutated sample also carrying TET2 lesions. Median VAF was 21%, with the exception of the oncodriver JAK2V617F, which showed a VAF > 50% in the reported case. Of note, of the four cases bearing lesions, 2/4 had multiple hits in different genes.While in recent years mutational analysis using NGS has proven to be able to differentiate clonal hematopoietic neoplasms from reactive processes in diagnostically difficult cases, we found somatic mutations in only 14.3% of patients who acceded to our hospital for idiopathic HE. More importantly, excluding the JAK2V617F-mutated case with an underlying MPN-Eo diagnosis, NGS was able to identify somatic mutations in only three cases, all older than 70 years. Consequently, the detection of these mutations in idiopathic HE patients should be interpreted with caution and only in the context of other supportive clinical-pathological findings.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"24 1","pages":"165"},"PeriodicalIF":3.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747587","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}