Clinical and Experimental Medicine最新文献

{"title":"The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.","authors":"Mahdis Abdar Esfahani, Nazli Servatian, Ali Jihad Hemid Al-Athari, Elaf Salah Mehdi Khafaja, Hamideh Rahmani Seraji, Hamed Soleimani Samarkhazan","doi":"10.1007/s10238-025-01783-z","DOIUrl":"10.1007/s10238-025-01783-z","url":null,"abstract":"<p><p>The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransferase inhibitors (e.g., azacitidine and decitabine), histone deacetylase inhibitors (e.g., vorinostat and romidepsin), and enhancer of zeste homologue 2 inhibitors (e.g., tazmetostat), demonstrates the potential to reverse aberrant epigenetic modifications and restoring normal cellular functions. Moreover, we highlight innovative therapeutic approaches, including combination therapies and CRISPR-based epigenetic editing tools, which are influencing the future of treatment for hematological malignancies. Despite promising results, challenges such as off-target effects, drug resistance, and the need for personalized approaches remain significant barriers to effective treatment. We emphasize that further study is required to improve delivery systems, comprehend resistance mechanisms and develop precision medicine strategies that can tailor therapies to individual patient profiles. By integrating benchside discoveries with clinical applications, this review aims to illuminate the transformative potential of epigenetic therapies in improving patient outcomes in hematology.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"230"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539231","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":"Identifying novel biomarkers for ankylosing spondylitis through proteomic profiling of serum-derived extracellular vesicles.","authors":"Soo-Eun Sung, Wook-Tae Park, Joo-Hee Choi, Young-In Kim, Min-Jung Ma, Wan-Suk Son, Sangbum Park, Ju-Hyeon Lim, Min-Soo Seo, Gun Woo Lee","doi":"10.1007/s10238-025-01718-8","DOIUrl":"10.1007/s10238-025-01718-8","url":null,"abstract":"<p><p>The objective of this study is to analyze the protein composition of extracellular vesicles (EVs) isolated from the serum of ankylosing spondylitis (AS) patients to identify potential biomarkers that could enable the early diagnosis and intervention of this condition. Serum samples were collected from AS patients and controls. EVs were isolated from these samples using ExoQuick® ULTRA solution, and their morphology, size, and concentration were analyzed using transmission electron microscopy and nanoparticle tracking analysis. Proteins within the EVs were identified and quantified through liquid chromatography-mass spectrometry (LC-MS/MS), followed by validation of key proteins using enzyme-linked immunosorbent assay (ELISA). Data were analyzed to identify proteins significantly upregulated in AS patients compared with the levels in controls. Here, through LC-MS/MS analysis, we demonstrated that Fibulin-1 (FBLN1), von Willebrand factor (VWF), complement factor H-related protein 2 (CFHR2), and lysozyme C (LYZ) expression were significantly upregulated in serum-derived EVs from AS patients compared with the levels in controls. These findings were further validated by ELISA, confirming the potential utility of serum-derived EVs as specific biomarkers for AS. The elevated levels of FBLN1, VWF, CFHR2, and LYZ in the EVs of AS patients represent promising candidates for biomarkers in the early diagnosis and treatment of AS. Further research should be performed to validate these findings and explore their clinical applicability.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"227"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539172","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":"SIRT1 as a masterful reciprocal regulator of molecular mechanisms and signaling pathways involved in tumor growth and expansion.","authors":"Mehrdad Hashemi, Neda Zali, Seyedeh Zahra Ghafarzadeh Dastjerdi, Bita Pakshad, Melika Aliahmadi, Nafiseh Sharifi, Kimia Sadat Esfahani, Fatemeh Sadat Kohandani, Sogand Chamanian, Fariba Abbasi, Faranak Jamshidian, Afshin Taheriazam, Mina Alimohammadi, Payman Rahimzadeh, Najma Farahani, Maliheh Entezari","doi":"10.1007/s10238-025-01759-z","DOIUrl":"10.1007/s10238-025-01759-z","url":null,"abstract":"<p><p>Sirtuin 1, which is more commonly identified as SIRT1, is a well-recognized NAD⁺-dependent histone and/or protein deacetylase that operates a wide range of cellular and molecular mechanisms involved in carcinogenic processes. SIRT1 not only regulates the primary mechanisms involved in tumorigenesis but also is responsible for controlling other processes, such as cell migration and metastasis, autophagy, and apoptotic flux, as well as chemotherapeutic resistance. It is well established that SIRT1 works at the upstream of signal transduction pathways, such as p53 signaling, together with FOXO mechanism, as well as the others. Indeed, SIRT1 by its deacetylase activity deacetylates different molecules in those signaling pathways and mostly causes a kind of blockade in the signaling of interest. Nonetheless, many aspects of SIRT1-cancer relationship are ambiguous, and more experiments should be performed for further uncovering of the concept. In the current review, we first highlight the major regulators of SIRT1 in cancer and then underscore key signal transduction pathways regulated by SIRT1. In the following, the role of SIRT1 will be discussed in tumor progression, from tumorigenesis to chemotherapeutic resistance, and at last, the contribution of SIRT1 to human cancers will be exemplified by some studies conducted in the field.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"225"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539174","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":"Preoperative ctDNA retains prognostic relevance beyond postoperative assessment in stage II-III colon cancer.","authors":"Giulia Chisari, Emanuele Martorana, Sofia Paola Lombardo, Gabriele Raciti, Raffaella Giuffrida, Alberto Bardelli, Domenico Scionti, Marzia Mare, Carolina Picardo, Enrica Deiana, Lorenzo Memeo, Cristina Colarossi, Giovanni Crisafulli, Stefano Forte","doi":"10.1007/s10238-025-01762-4","DOIUrl":"10.1007/s10238-025-01762-4","url":null,"abstract":"<p><p>In cancer patients, only a small fraction of circulating cell-free DNA (cfDNA) consists of circulating tumor DNA (ctDNA), which contains tumor-specific features. Detecting ctDNA in peripheral blood through liquid biopsy offers a safe, noninvasive alternative to traditional tissue biopsy, with the added benefit of enabling repeated testing over time. This study investigates the potential of liquid biopsy as an innovative and noninvasive prognostic tool for patients with stage II-III colon cancer. Specifically, we analyzed the presence of cfDNA harboring tumor-specific mutations, previously identified in tumor tissue via next-generation sequencing (NGS), both before and after therapeutic surgery. Our aim was to assess its predictive value for relapse, ultimately guiding therapeutic decisions and improving patient outcomes. Our results demonstrate that the presence of ctDNA before surgery was significantly associated with disease relapse, indicating its potential as a predictive biomarker. In this cohort, ctDNA detection after surgery, during adjuvant chemotherapy, did not maintain the same predictive value. This suggests that preoperative ctDNA analysis may provide critical prognostic information, while post-surgical ctDNA monitoring, in this specific setting, may be influenced by treatment dynamics. In conclusion, we found that combining NGS profiling of the primary tumor tissue with droplet digital PCR (ddPCR)-based analysis of cfDNA provides a comprehensive approach to therapy monitoring in stage II-III colon cancer patients. Liquid biopsy offers valuable insights into treatment response and disease progression while serving as a noninvasive and repeatable method for routine clinical care.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"222"},"PeriodicalIF":3.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526648","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":"Functional remodeling of tissue-resident macrophages leads to distinct immune microenvironment evolution and clinical manifestations in lung adenocarcinoma.","authors":"Yanqi Li, Li Jiang, Xiaobing Liu, Jigang Dai, Quanxing Liu","doi":"10.1007/s10238-025-01760-6","DOIUrl":"10.1007/s10238-025-01760-6","url":null,"abstract":"<p><p>Given the indispensable role in extracellular matrix remodeling and immunosuppressive microenvironment formation, the importance of tissue-resident macrophages (TRM) in the occurrence of early-stage cancer has been constantly mentioned. And it is noteworthy that the widespread application of low-dose CT (LDCT) has resulted in a marked increase in the proportion of early-stage patients for lung cancer in recent years, including plenty adenocarcinoma in situ (AIS) patients with ground-glass nodule (GGN) feature on imaging. The group of GGN-like AIS (AIS with ground-glass nodule feature) patients have gradually become a clinical challenge for thoracic surgeons, as surgically removed considered justified only when there is evident malignant progression risk. However, despite many teams, including ours, have proposed possible strategies for non-invasive and efficient assessing the malignant risk of GGN-like AIS patients, the unclear mechanism of the malignant progression for GGN-like AIS toward early-stage lung adenocarcinoma (LUAD) limits further clinical application and optimization. In this study, utilizing transcriptome, we classified TCGA-LUAD patients into distinct TRM functional states and conducted a comprehensive analysis of the physiological significance behind each subtype. Utilizing single-cell data, we have well mapped the results of transcriptome analysis at the cellular level and ultimately identified that KRT6A⁺ Ep may be the key epithelial subpopulation for the functional remodeling of TRM. Our study deepened the understanding of the malignant transformation mechanism of GGN-like AIS, as well as provided referential indicators for more personalized treatment and management of LUAD patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"223"},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526646","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":"Integrative regression modeling of insulin sensitivity, resistance, and beta-cell dysfunction in predicting female infertility: a cross-sectional NHANES study.","authors":"Seyed Sobhan Bahreiny, Mohammad Ali Khaksar, Negin Karamali, Mohammad Reza Dabbagh, Akbar Hoseinnejad, Reza Mohammadpour Fard, Zahra Sadat Bahreiny, Mojtaba Aghaei, Tannaz Sakhavarz, Mehdi Zahedian","doi":"10.1007/s10238-025-01755-3","DOIUrl":"10.1007/s10238-025-01755-3","url":null,"abstract":"<p><p>Insulin sensitivity, resistance, and pancreatic beta-cell function play key roles in metabolic and reproductive health. Despite the known role of glucose-insulin homeostasis in female reproductive health, the association and regression modeling of estimated glucose disposal rate (eGDR), homeostatic model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-β), and insulin disposition index (Insulin-DI) with female infertility remain unclear. This cross-sectional study aimed to assess the associations between insulin-related indices and female infertility. This study examined data from 2832 women aged 18-45 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-2023 cycles. To evaluate the associations between four insulin-related indices and infertility, multivariable logistic regression, generalized additive models, and threshold effect analyses were applied, while controlling for relevant sociodemographic, lifestyle, and metabolic confounders. Furthermore, integrated meta-analysis across models, distributional analysis, subgroup and interaction analyses were conducted to explore potential effect modifications. eGDR showed a strong inverse association with infertility across all models (OR range: 0.636-0.85, p < 0.001), with a significant nonlinear pattern (p = 0.003) and a threshold at 4.59. HOMA-IR was positively associated in unadjusted models (OR = 1.147, p < 0.001) but lost significance after full adjustment. HOMA-β showed a weak positive association (OR = 1.003, p = 0.0227), while Insulin-DI was inversely related to infertility only in unadjusted models. Subgroup analyses revealed significant effect modifications by BMI and age, especially for eGDR and HOMA-IR. Reduced insulin sensitivity, as indicated by lower eGDR, is strongly linked to higher infertility risk. HOMA-IR and Insulin-DI also show threshold-based nonlinear associations.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"224"},"PeriodicalIF":3.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526647","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":"Integrated analysis of CD30 detection methodologies and synergistic drug combinations for optimizing brentuximab vedotin therapy in lymphoma.","authors":"Mingyu Ye, Tao Wang, Zhiqiang Song, Xuefei Liu, Ping Liu, Ling Zhang, Gusheng Tang, Miaoxia He, Na Liu, Jianmin Yang","doi":"10.1007/s10238-025-01765-1","DOIUrl":"10.1007/s10238-025-01765-1","url":null,"abstract":"<p><p>Brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate, has shown significant efficacy in CD30-positive lymphoma. However, the relationships between CD30 expression levels and BV efficacy remains unclear. In this study, we first evaluated the reliability of CD30 detection by immunohistochemistry (IHC) and found that flow cytometry (FCM) offers higher sensitivity and accuracy in assessing CD30 expression. Therefore, FCM may serve as a more effective method for evaluating CD30 levels. Furthermore, we confirmed a positive correlation between CD30 expression levels and BV efficacy. However, even when BV was applied to tumor cells with 100% CD30 expression, its anti-tumor activity did not reach complete eradication, highlighting the need for synergistic combination therapies. To address this, we conducted high-throughput screening (HTS) and identified auranofin and napabucasin as synergistic agents that enhance the efficacy of BV. These findings not only highlight the advantages of FCM for CD30 detection, but also provide valuable insights into combination strategies to optimize the therapeutic potential of BV.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"221"},"PeriodicalIF":3.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505031","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":"Differential response of patient-derived primary glioblastoma cells to metabolic and adhesion inhibitors.","authors":"Rasha Rezk, Fikret Basar, John Mediavillo, Rebecca Donaldson, Colin Watts, Kristian Franze, Alexandre J Kabla","doi":"10.1007/s10238-025-01736-6","DOIUrl":"10.1007/s10238-025-01736-6","url":null,"abstract":"<p><p>This study aims to investigate the cellular response of Glioblastoma (GBM) to adhesion and metabolic inhibitors, focusing on cell migration and matrix adhesion properties. GBM is the most common incurable brain tumor. Despite decades of research into GBM's chemical and molecular classification, identifying mechanisms of drug resistance has been challenging. Studies on inhibitors targeting cancer cell migration and proliferation rarely consider the heterogeneous migration properties among cells, which may impact patient responses to treatment. In this work, tissue samples were obtained from spatially distinct locations with different 5-aminolevulinic acid (5-ALA) fluorescent intensities-including strongly fluorescent tumor cores, a weakly fluorescent tumor rim, and non-fluorescent tumor margins. These samples were previously shown to be associated with significantly different motility and adhesion properties. We tested the response of tumor cells to adhesion and metabolic inhibitors using metabolic MTT and Cell Titer Glo viability assays, respectively. We also monitored cell survival using time-lapse microscopy, while culturing them on low-modulus polydimethylsiloxane (representing the stiffness of brain tissue). Metabolic viability assays revealed substantial heterogeneity in drug potency across cells from different regions of the tumor. Highly fluorescent tumor core cells were significantly more resistant to an F0F1 ATP synthase inhibitor (Gboxin), and a FAK inhibitor (GSK2256098), while their proliferation ceased post-treatment in vitro. In contrast, cells derived from non-fluorescent tumor margins exhibited higher potency for the ATP synthase inhibitor (Gboxin), but their proliferation persisted post-treatment. Our study demonstrates a correlation between the adhesive and migration properties of cells and their sensitivity to therapeutics in different regions of the tumor within individual patients and between patients with GBM.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"220"},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494995","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":"Microvesicle inhibition enhances the therapeutic effects of ATRA in acute promyelocytic leukemia cells via changes in miRNAs: the promising antileukemic potential of imipramine.","authors":"Haniyeh Kariminejad-Farsangi, Roohollah Mirzaee Khalilabadi, Ali Afgar, Mahdieh Mirzaie, Hajar Mardani Valandani","doi":"10.1007/s10238-025-01763-3","DOIUrl":"10.1007/s10238-025-01763-3","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) represent an essential role in cancer progression through intercellular communication. Therefore, the use of EV formation inhibitors could be a profitable therapeutic strategy in various types of cancer, including leukemia. Imipramine, a tricyclic antidepressant, can block EV formation by inhibiting acid sphingomyelinase. Additionally, other crucial players in cancer progression are microRNAs, which regulate molecular mechanisms at the post-transcriptional level. Here, to potentiate the therapeutic effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), we investigated the effect of imipramine as a microvesicle inhibitor in combination with ATRA for the treatment of APL-derived NB4 cells. Our results declared that imipramine reduced the viability and metabolic activity of ATRA-treated NB4 cells after 48 h. In addition, flow cytometry results highlighted that imipramine induced cytotoxicity through G2/M phase arrest followed by apoptosis. Moreover, we discovered that the antileukemic effects of imipramine were associated with inhibiting microvesicle release and miRNA alteration. Based on bioinformatics methods, we predicted two miRNAs, including hsa-miR-4498 and hsa-miR-3156-5p, which target PML. Additionally, we selected miR-23a-5p, miR-19a-3p, and miR-181b-5p based on relevant studies and subsequently predicted their target genes. The real-time PCR results revealed that the expression level of these miRNAs increased after treatment with imipramine. Moreover, functional enrichment analysis of target genes demonstrated that these genes are involved in cancer-related pathways, including MAPK, FOXO, AMPK, and cellular senescence. Given the significant efficacy of imipramine in potentiating the anti-tumor effects of chemotherapeutic drugs, it can be considered as a potential treatment agent for APL.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"217"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483403","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":"Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances.","authors":"Yan Feng, Yaxian Ma, Tongjuan Li, Min Liu, Zetong Hong, Qing Yin, Miao Zheng","doi":"10.1007/s10238-025-01754-4","DOIUrl":"10.1007/s10238-025-01754-4","url":null,"abstract":"<p><p>Angioimmunoblastic T-cell lymphoma (AITL), a rare subtype of peripheral T-cell lymphoma (PTCL) with regional differences, originates from follicular T helper (Tfh) cells and is characterized by significant immunological involvement. The tumor microenvironment (TME) in AITL is complex, primarily composed of T cells, B cells, plasma cells, follicular dendritic cells and high endothelial venules. Genetically, AITL exhibits the characteristics of TET2 and DNMT3A mutations in hematopoietic stem cells, while RHOA and IDH2 mutations are detected in the Tfh cells. Subsequently, Tfh cells begin to release various chemokines and cytokines to regulate the intricate network of interactions with TME promoting development of AITL. Diagnosis remains challenging for AITL due to diverse clinical presentations and laboratory features resembling changes seen in multiple benign diseases. Several predictive models have been proposed; however, overall prognosis for AITL remains poor. Treatment strategies should be based on the patient's age, physical condition, and comorbidities. Participation in clinical trials is recommended as an initial treatment strategy. Autologous stem-cell transplantation (ASCT) for AITL still remains to be a subject of ongoing debate. Numerous multi-phase clinical trials have been carried out for relapsed/refractory (R/R) AITL. Moreover, CAR-T and CAR-NK therapy represents promising avenues that are worthy of further exploration for the treatment of AITL.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"218"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483401","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}