Clinical and Experimental Medicine最新文献

{"title":"Angiogenesis-related gene signature for prognostic prediction and immune microenvironment characterization in diffuse large B-cell lymphoma.","authors":"Chuanming Lin, Shuiling Xie, Menger Wang, Bin Yang, Jianzhen Shen","doi":"10.1007/s10238-025-01628-9","DOIUrl":"https://doi.org/10.1007/s10238-025-01628-9","url":null,"abstract":"<p><p>Diseases often result from multiple factors, and angiogenesis-related genes (ARGs) have been demonstrated to be associated with cancer. However, their role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. ARGs associated with DLBCL prognosis were identified utilizing Cox regression and LASSO analyses. A prognostic model was constructed based on 7 ARGs, and its biological function was analyzed. Differences in the tumor immune microenvironment based on the prognostic signature were evaluated. Finally, DLBCL cell experiments confirmed the differential expression of genes in DLBCL. The prognostic value of ARGs in DLBCL patients was comprehensively analyzed for the first time, identifying 7 ARGs with prognostic significance. A prognostic risk model was constructed based on these 7 ARGs and validated on an independent external DLBCL dataset. In DLBCL patients, this prognostic feature was an independent risk factor and significantly correlated with clinical characteristics. This feature was also associated with the immune microenvironment of DLBCL. DLBCL cell experiments confirmed significant expression of the 7 ARGs in DLBCL cells. This research provides a fundamental theoretical basis for improving the diagnosis and treatment of DLBCL in clinical practice.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"108"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810637","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":"Biosimilars versus biological therapy in inflammatory bowel disease: challenges and targeting strategies using drug delivery systems.","authors":"Ahmed Aljabri, Ghareb M Soliman, Yasmin N Ramadan, Mohammed A Medhat, Helal F Hetta","doi":"10.1007/s10238-025-01558-6","DOIUrl":"10.1007/s10238-025-01558-6","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a multifactorial illness with a climbing prevalence worldwide. While biologics are commonly prescribed especially for severe cases, they may worsen patients' outcomes due to financial burden. Consequently, there has been an increased focus on biosimilars to improve overall disease outcomes by maintaining similar efficacy and safety while minimizing the cost of therapy. Infliximab-dyyb was the first biosimilar approved by US-FDA for IBD. Since that, the US-FDA approved 14 biosimilars with different mechanisms of action and different routes of administration for IBD patients (four infliximab biosimilars, nine adalimumab biosimilars, and most recently one ustekinumab biosimilar). It should be noted that more biologics are in the pipeline as golimumab and natalizumab patents are set to expire in the near future, and biosimilars are now in pre-clinical to phase 3 trials. Different studies have evaluated biologics' effectiveness and safety and concluded that the majority of available biosimilars are efficacious and have similar adverse effect profiles compared to their reference biologics. It is worth mentioningthat post-marketing surveillance reports revealed some risks associated with biosimilars which should be taken into consideration in future research and clinical trials to avoid health hazards. Most biologics and biosimilars are administered parenterally which results in several drawbacks such as raised risk of infections, hypersensitivity, autoimmunity, development of malignancies, liver toxicity as well as worsening of heart failure. Several drug delivery systems based on passive and active targeting mechanisms are under active investigation to overcome these limitations. This review sheds light on the emergence of biologics and biosimilars as alternatives in IBD management, the differences between them, challenges and risks, and future perspectives in IBD therapy and new trends in drug delivery systems.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"107"},"PeriodicalIF":3.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787775","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":"PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.","authors":"Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J M Sullman, Nahid Eskandari","doi":"10.1007/s10238-025-01641-y","DOIUrl":"10.1007/s10238-025-01641-y","url":null,"abstract":"<p><p>The phenomenon of upregulated programmed death-ligand 1 (PD-L1) expression is common in numerous human malignancies. The overexpression of PD-L1 significantly contributes to immune evasion because its interaction with the PD-1 receptor on activated T lymphocytes impairs anti-tumour immunity by neutralizing T cell stimulatory signals. Furthermore, beyond its immunological interface, PD-L1 possesses intrinsic capabilities that directly modulate oncogenic processes, fostering cancer cell proliferation and survival. This dual function of PD-L1 challenges the efficacy of immune checkpoint inhibitors and highlights its possible application as a direct target for therapy. Recent discoveries concerning the cancer cell-intrinsic signalling pathways of PD-L1 have significantly enhanced our understanding of the pathological implications linked to its tumour-specific expression. These entail the orchestration of tumour proliferation and viability, maintenance of cancer stem cell-like phenotypes, modulation of immune responses, as well as impacts on DNA repair mechanisms and transcriptional regulation. This review aims to deliver an exhaustive synthesis of PD-L1's molecular underpinnings alongside its clinical implications in a spectrum of cancers, spanning both solid neoplasms and haematological disorders. It underscores the necessity for an integrated understanding of PD-L1 in further refining therapeutic strategies and improving patient outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"106"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779223","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":"Venetoclax-based low-intensity chemotherapy in the salvage treatment of relapsed/refractory T-cell acute lymphoblastic leukemia.","authors":"Fangfei Xu, Xingshuo Bao, Wei Huang, Kuangguo Zhou","doi":"10.1007/s10238-025-01638-7","DOIUrl":"10.1007/s10238-025-01638-7","url":null,"abstract":"<p><p>T-cell acute lymphoblastic leukemia (T-ALL) is a very rare hematological malignancy with a poor prognosis. Conventional cytotoxic regimens have exhibited poor tolerance in clinical practice. Preclinical researches, sparse case reports, and small-scale single-arm studies showed that venetoclax-based salvage chemotherapy had a promising clinical efficacy. However, to date, no case-control studies or prospective trials in relapsed/refractory T-ALL have been conducted to compare venetoclax-based therapies with conventional cytotoxic chemotherapies, owing to the disease's rarity and the challenging treatment landscape. We conducted a retrospective case-cohort study comparing venetoclax-based low-intensity chemotherapy with conventional cytotoxic chemotherapies in the treatment of relapsed/refractory T-ALL. Our results indicated that venetoclax-based chemotherapy achieved comparable outcomes with heavily cytotoxic agents in complete remission rates (58.3% vs. 41.7%, P = 0.759), renal dysfunction (0% vs. 16.7%, P = 0.478), infections (50.0% vs. 75.0%, P = 0.400), and thrombocytopenia duration (17.0 vs. 14.5 days, P = 0.434) between the venetoclax and non-venetoclax cohorts. Additionally, venetoclax-treated patients experienced fewer non-hematological adverse events, such as elevated liver enzymes than conventional cytotoxic chemotherapies (0% vs. 41.6%, P = 0.014), which may be attributed to reduced use of intensive cytotoxic agents like pegylated asparaginase in the venetoclax cohort. Venetoclax-based low-intensity chemotherapy might have a relatively favorable safety profile and non-inferior efficacy compared to conventional cytotoxic regimens. Therefore, venetoclax-based low-intensity chemotherapy might become a potential treatment option, especially for frail patients or those with poor hepatic function who were unable to tolerate multiple cytotoxic therapies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"104"},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763234","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":"Evaluation of the efficacy and safety of belimumab and telitacicept in patients with systemic lupus erythematosus: results from a retrospective, observational study.","authors":"Tianxiao Feng, Manyu Zhang, Jieying Wang, Yang Li, Yang Cui","doi":"10.1007/s10238-025-01640-z","DOIUrl":"10.1007/s10238-025-01640-z","url":null,"abstract":"<p><p>This investigation aimed to evaluate the efficacy and safety of belimumab and telitacicept in active systemic lupus erythematosus (SLE) and to explore potential predictors within a treat-to-target paradigm. 101 individuals were retrospectively enrolled at Guangdong Provincial People's Hospital between January 2021 and December 2023, receiving either belimumab (n = 50) or telitacicept (n = 51) in conjunction with standard therapy for more than 24 weeks. Key clinical endpoints were evaluated, with lupus low disease activity state (LLDAS) as the primary outcome. Multivariate analysis was employed to investigate factors associated with failure to attain LLDAS. Baseline characteristics were balanced in both groups after propensity score-based inverse probability of treatment weighting. At 24 weeks, the rates of attainment of LLDAS were 54.86% in the telitacicept group and 33.13% in patients receiving belimumab (p = 0.048). A larger proportion of patients receiving telitacicept attained prednisone dosages of ≤ 7.5 mg/day (p = 0.012). Improvements in complement C4 levels and the occurrence of severe hypogammaglobulinemia were more pronounced among patients receiving telitacicept, with no differences in SLE Responder Index 4, DORIS remission, and renal response. Treatment with telitacicept (OR = 0.80, p = 0.032) and elevated levels of complement C3 (OR = 0.63, p = 0.003) were associated with a decreased risk of failing to achieve LLDAS. No severe adverse events were documented in both groups. Both belimumab and telitacicept displayed satisfactory effectiveness and safety profiles. Our findings imply telitacicept may offer potential benefits associated with the early attainment of LLDAS and reduced glucocorticoid exposure. Restricted by the observational design, the findings require further validation in prospective studies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"105"},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763229","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":"Unexpectedly high prevalence of familial Mediterranean fever in Slovakia.","authors":"M Jesenak, E Malicherova Jurkova, A Bobcakova, K Hrubiskova, O Petrovicova, L Kapustova, R Kosturiak, T Dallos, A Markocsy","doi":"10.1007/s10238-025-01634-x","DOIUrl":"10.1007/s10238-025-01634-x","url":null,"abstract":"<p><p>Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome among all monogenic autoinflammatory diseases. It is characterised by recurrent, self-limited fever attacks of short duration, polyserositis symptoms, and elevated acute-phase reactants. FMF has the highest prevalence in the Eastern Mediterranean region. The first descriptions of FMF cases in Central Europe date back to 2014. The prevalence in the Central European region was previously estimated at 1:465,500 in the paediatric population, with data on adult prevalence lacking. Patients with FMF who fulfilled Eurofever/PRINTO diagnostic criteria were included in the study. Massive parallel sequencing of clinical exome with evaluation of virtual panel for genes associated with inborn errors of immunity and autoinflammatory conditions was used in the vast majority of the patients. Statistical analysis of clinical and laboratory manifestation was performed. The prevalence of FMF in the Slovak population of the present study was 1:48,224 (1:41,348 in children and adolescents), which is significantly higher than expected. The most common variant in our cohort was M694V, present in 52.0% of alleles. Variant K695R was observed in 29.9% which is higher than reported in the other FMF cohorts. Abdominal pain and fever were the most prevalent clinical symptoms, although up to one-third of patients also experienced atypical symptoms such as tonsillitis or cervical lymphadenopathy. This paper provides the first comprehensive analysis of the Slovak National FMF cohort, including epidemiological data, clinical manifestations, and genetic background. Our data could contribute to the general knowledge about FMF characteristics in the underreported regions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"101"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751518","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":"Meta-analysis of the comparative efficacy and safety of new drugs in combination with chemotherapy in primary plasmoblastic lymphoma.","authors":"Bingling Guo, Xi Quan, Zailin Yang, Jieping Li, Yao Liu","doi":"10.1007/s10238-025-01636-9","DOIUrl":"10.1007/s10238-025-01636-9","url":null,"abstract":"<p><p>To systematically evaluate the efficacy and safety of regimens combining new drugs (bortezomib, etc.) with chemotherapy in the treatment of plasmaoblastoid lymphoma (PBL). PubMed, Embase, Web of Science, American Society of Hematology Annual Meeting Proceedings, Cochrane Controlled Trials Center Registry, Cochrane Library, Science Citation Index, and meeting abstracts were searched for quality evaluation based on Cochrane Risk and Jadad scores and other assessment tools. Patients were divided into subgroup 1 (traditional treatment vs. no treatment) and subgroup 2 (traditional treatment vs. combination of new drugs) based on medication use, and Revman 5.4 software was applied for statistical analysis. A total of 12 papers were included, including 410 patients with PBL. Meta-analysis results: the objective remission rate (ORR) of patients in the combination of new drugs group was higher than that of the traditional treatment group [56.8% (25/44) vs. 70.2% (66/94); OR = 2.18, 95%CI 1.58-2.78, P = 0.002 < 0.05], and the progression-free survival (PFS) rate of patients in the combination of new drugs group was higher than that of the traditional treatment group. the progression survival (PFS) was better than traditional treatment group (HR = 2.22, 95%CI 1.71-2.90, P < 0.001), and the heterogeneity between the results of each study I = 95%; there was no statistically significant difference between the two groups in terms of overall survival (OS) (HR = 1.81, 95%CI 0.44-7.46, P = 0.41), and grade 3-4 adverse events (AE) (HR = 0.85, 95%CI 0.27-7.46, P = 0.002 < 0.05). 95%CI 0.27-2.71, P = 0.78) were not statistically different. The regimen combining new drugs is an effective means to improve the prognosis of PBL, with better ORR and PFS than the traditional regimen, and there is no statistically significant difference between the two adverse events. However, the small sample size of this study increases the possibility of bias and the results need to be treated with caution.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"103"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751494","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":"N6-methyladenosine-mediated upregulation of H19 promotes resistance to bortezomib by modulating the miR-184/CARM1 axis in multiple myeloma.","authors":"Gang Wang, Wenping Wu, Donghua He, Jiaheng Wang, Hongwei Kong, Wenjun Wu","doi":"10.1007/s10238-025-01624-z","DOIUrl":"10.1007/s10238-025-01624-z","url":null,"abstract":"<p><p>Malignant plasma cell proliferation characterizes multiple myeloma (MM), a hematologic disease. Bortezomib (BTZ) is a protease inhibitor that has been approved for the treatment of MM. Nevertheless, the effectiveness of BTZ is frequently impeded by drug resistance, and the mechanisms responsible for this phenomenon remain incompletely understood. A growing body of evidence indicates that N6-methyladenosine (m6A) plays crucial roles in a wide range of biological functions. However, the impact of m6A on the response of MM cells to BTZ is poorly understood. In our recent research, we discovered that METTL3 facilitated the m6A alteration of lncRNA H19, providing MM cells with resistance to BTZ. Additional examination revealed that H19 functioned as a sponge to negatively regulate the expression of miR-184 in MM cells. Furthermore, we discovered that H19 binds to miR-184, a tumor suppressor, in MM cells. In MM cells, miR184 can suppress the expression of CARM1 by targeting its 3'-UTR. In conclusion, rescue trials have validated the significance of the METTL3/H19/miR-184/CARM1 pathway in determining the susceptibility of cells to BTZ. Consequently, directing efforts toward this pathway could prove to be a powerful approach for enhancing the effectiveness of BTZ for MM therapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"102"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751510","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":"Undifferentiated connective tissue disease: the diagnoses critically revised-experience of a single center.","authors":"Ilaria Cavazzana, Paolo Semeraro, Cesare Tomasi, Elena Sofia Kessler, Silvia Piantoni, Alessia Caproli, Micaela Fredi, Franco Franceschini","doi":"10.1007/s10238-025-01614-1","DOIUrl":"10.1007/s10238-025-01614-1","url":null,"abstract":"<p><p>Although anti-nuclear antibodies (ANA) are considered the main entry criteria for a diagnosis of undifferentiated connective tissue disease (UCTD), many patients show different rate of ANA positivity and questionable diagnoses. Aim of the study was to revise the UCTD diagnoses and analyse the main predictors of evolution in a monocentric cohort. We retrospectively revised the diagnoses of 331 ANA positive patients, with at least one year of follow-up, classified as UCTD from 2009 and 2017. The diagnosis of UCTD was confirmed in 180 cases (54.4%). The evolution occurred in 18% of cases, after a follow-up of 6.9 (SD: 4.4) years. Raynaud's phenomenon (RP) (OR: 2.39), puffy hands (OR: 6.3), anti-ENA (OR: 2.34), anti-Topoisomerase I antibodies (OR: 4.93), rheumatoid factor (RF) (OR: 2.86) were associated with evolution. Evolution in Systemic Lupus Erythematosus (SLE) occurred in 5 patients (2.78%) and associated with the addition of new autoantibodies, compared with other evolutions (p: 0.034; OR: 12; 95CI: 1.4-103.4). Evolution in Systemic Sclerosis and pSS was found in 14 (7.8%) and 8 cases (4.4%), respectively. Puffy hands and RF positivity as the predictors of SSc and pSS evolution, respectively. A confirmed diagnosis of UCTD, according with the available criteria, was assessed in about a half patients. The occurrence of puffy hands since the onset defines a patient with a potential evolution into SSc, while the addition of new specific autoantibodies represents a typical \"fingerprint\" of patients developing SLE. Trial registration: Studio ANACTD np 1318.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"100"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742417","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":"YY1-induced transcription of AKR1C3 activates the Hedgehog signalling pathway to enhance lenalidomide resistance and glycolytic activity in multiple myeloma cells.","authors":"Yang Chen, Aijia Zhang, Yuan Wang, Daoda Qi, Chengyi Peng, Zihao Liang, Jingjing Guo, Yan Gu","doi":"10.1007/s10238-025-01619-w","DOIUrl":"10.1007/s10238-025-01619-w","url":null,"abstract":"<p><p>Lenalidomide (LEN) is a mainstay for treating multiple myeloma (MM), but its efficacy is often limited by resistance. We investigated the interaction between aldo-keto reductase family 1 member C3 (AKR1C3) and Yin Yang 1 (YY1) and their roles in LEN resistance. We induced LEN-resistant MM cell lines (H929R and U266R). Loss- or gain-of-function assays of AKR1C3 and YY1 were used to analyse the half maximal inhibitory concentration (IC₅₀) values, cell senescence, DNA damage, and glycolytic activity under LEN treatment. Chromatin immunoprecipitation was used to determine the interaction between YY1 and AKR1C3. As results, AKR1C3 and YY1 were upregulated in H929R and U266R cells. AKR1C3 silencing decreased the LEN's IC₅₀, slowed cell growth, enhanced senescence and DNA damage, reduced metabolic reprogramming. YY1 activated the transcription of AKR1C3 by binding to its promoter region. Similarly, silencing YY1 enhanced LEN sensitivity, suppressed glycolysis, and was counteracted by AKR1C3 overexpression. Mechanistically, YY1-AKR1C3 activated the Hedgehog pathway; fluticasone reversed the effects of AKR1C3 silencing on LEN resistance and glycolysis in H929R and U266R cells. Overall, YY1 activates AKR1C3 transcription and the Hedgehog pathway to increase LEN resistance and glycolytic activity in MM cells.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"99"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742449","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}