Medical Oncology最新文献

{"title":"Mechanistic insights and nanomedicine innovations of oligomeric proanthocyanidin in precision oncology: Ablating self-renewal capacity of metastatic cancer stem cells via multi-pathway modulation.","authors":"Tushara Saha, Srijoni Banerjee, Kanu Priya, Shiv Kumar Giri, Mithul Rajeev, Shareen Singh, Sarvesh Rustagi, Debasmita Bhattacharya, Moupriya Nag, Harjot Singh Gill, Dibyajit Lahiri","doi":"10.1007/s12032-025-02992-y","DOIUrl":"https://doi.org/10.1007/s12032-025-02992-y","url":null,"abstract":"<p><p>Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a). Furthermore, OPCs reorganize the tumor microenvironment by suppressing CSC markers (CD44, CD133, ALDH1, EpCAM) and reconstituting immune surveillance. Preclinical in-vitro and in-vivo models in colorectal, breast, and prostate cancers show OPC-mediated CSC elimination, apoptosis, and chemosensitization with minimal systemic toxicity. Emerging advances-redox-sensitive and pH-sensitive nanocarriers, exosome-based delivery, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 functional screens, and patient-derived organoids-present revolutionary solutions to overcome bioavailability bottlenecks and deliver precision-targeted therapies. These advances highlight the promise of OPCs as next-generation, multi-targeted anti-CSC oncology therapeutics.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"467"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030019","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":"Deciphering the molecular landscape of acute myeloid leukemia initiation and relapse: a systems biology approach.","authors":"Atefeh Bahmei, Hanieh Fadakar, Gholamhossein Tamaddon","doi":"10.1007/s12032-025-03003-w","DOIUrl":"https://doi.org/10.1007/s12032-025-03003-w","url":null,"abstract":"<p><p>Acute Myeloid Leukemia (AML) patient-derived Mesenchymal Stem Cells (MSCs) behave differently than normal ones, creating a more protective environment for leukemia cells, making relapse harder to prevent. This study aimed to identify prognostic biomarkers and elucidate relevant biological pathways in AML by leveraging microarray data and advanced bioinformatics techniques. We retrieved the GSE122917 dataset from the NCBI Gene Expression Omnibus and performed differential expression analysis (DEA) within R Studio to identify differentially expressed genes (DEGs) among healthy donors, newly diagnosed AML patients, and relapsed AML patients. Data normalization and DEA were achieved using the PLIER method and Plotrix package, with quality assessment performed through visual box plots. Functional enrichment analyses and KEGG pathway analysis illuminated the biological processes associated with DEGs. Network interactions were visualized using Cytoscape software. Survival analysis is performed through Kaplan-Meier plotter. Our analysis revealed a significant downregulation of NCAPG, UBE2C, CDC20, and CDK1, alongside the upregulation of SPP1, as key genes implicated in both the initiation and relapse phases of AML. Survival analysis indicated that lower expression levels of NCAPG, UBE2C, CDC20, and CDK1, and higher levels of SPP1, were correlated with poorer event-free survival (EFS). Additionally, the study highlighted the cell cycle as pivotal in leukemia initiation and progression, while the p53 pathway emerged as critical during the relapse phase. Our findings suggest that NCAPG, UBE2C, CDC20, CDK1, and SPP1 may serve as prognostic biomarkers for AML management, especially through their interaction with the p53 pathway in disease progression. These insights underscore the potential for targeting the p53 pathway and integrating these biomarkers to enhance outcomes for AML patients.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 11","pages":"468"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030090","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":"NPY-functionalized niosomes for targeted delivery of margatoxin in breast cancer therapy.","authors":"Zohre Eftekhari, Mohsen Chiani, Fatemeh Kazemi-Lomedasht","doi":"10.1007/s12032-025-03026-3","DOIUrl":"10.1007/s12032-025-03026-3","url":null,"abstract":"<p><p>Neuropeptide Y (NPY) and the voltage-gated potassium channel Kv1.3 are closely associated with breast cancer progression and apoptosis regulation, respectively. NPY receptors (NPYRs), which are overexpressed in breast tumors, contribute to tumor growth, migration, and angiogenesis. In parallel, Kv1.3 plays a pivotal role in mitochondrial-mediated apoptosis, and its inhibition can induce cancer cell death. To exploit these mechanisms, we developed and characterized a novel niosomal drug delivery system encapsulating margatoxin (MgTx), a potent Kv1.3 inhibitor, and functionalized with NPY for targeted breast cancer therapy. Niosomes were synthesized via a modified thin-film hydration method and decorated with NPY peptides to enable selective binding to NPYR-overexpressing cancer cells. Physicochemical analyses using dynamic light scattering (DLS), atomic force microscopy (AFM), and field emission scanning electron microscopy (FESEM) confirmed a nanoscale size range (134-161 nm), spherical morphology, and successful surface modification. The system demonstrated high encapsulation efficiency, prolonged stability at 4°C, and sustained MgTx release over 72 h. In vitro cytotoxicity studies revealed that NPY-decorated MgTx-loaded niosomes significantly reduced the viability of MCF-7 and MDA-MB-231 breast cancer cells while exerting minimal toxicity on non-tumorigenic MCF-10A cells. qRT-PCR analysis indicated upregulation of pro-apoptotic genes (Bax, Caspase-3) and downregulation of anti-apoptotic Bcl2, confirming induction of apoptosis in treated cancer cells. These findings highlight the potential of NPY-functionalized niosomes as an effective and selective nanoplatform for targeted breast cancer therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"465"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023653","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":"Pterostilbene as a promising natural anticancer agent in gynecological cancers.","authors":"Tayyeba Rehman, Yhiya Amen","doi":"10.1007/s12032-025-03013-8","DOIUrl":"10.1007/s12032-025-03013-8","url":null,"abstract":"<p><p>Gynecological cancer, encompassing cancers such as endometrial and cervical cancer, is a growing concern worldwide, with a rising incidence and significant impact on women's health. Pterostilbene (PT), a natural compound, has shown promising therapeutic potential in gynecological cancer treatment. This review aims to summarize the current state of knowledge on PT's effects in gynecological cancer, focusing on its molecular mechanisms, preclinical studies, and clinical trials. A comprehensive literature search was conducted using databases, such as Google Scholar, PubMed, Wiley Online Library, Scopus, and Web of Science, covering studies published over the last 10 years (2015-2025). The search focused on PT's therapeutic potential in gynecological cancer, including its synergistic action with other therapies or natural compounds. The review highlights PT's ability to modulate key signaling pathways, induce apoptosis, and inhibit cell cycle progression in endometrial carcinoma cells and cervical cancer cells. Preclinical studies demonstrate PT's efficacy in reducing tumor size and enhancing anti-tumor activity when pterostilbene (PT) is combined with megestrol acetate (MA). Clinical trials suggest that PT combined with MA may be a promising therapeutic strategy for endometrial cancer treatment. Overall, this review provides a comprehensive overview of PT's therapeutic potential in gynecological cancer and highlights its promise as a potential treatment option. Further research is needed to fully establish PT's efficacy and safety in gynecological cancer patients. Notably, our literature search did not yield sufficient studies related to vulvar or vaginal cancers, highlighting a significant gap in the current research landscape.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"466"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023629","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 microbiome-cancer axis as a hidden contributor to early-onset tumorigenesis.","authors":"Azfar Jamal, Mohammad Azhar Kamal, Yaser E Alqurashi, Esam S Al-Malki, Mohammed M Naiyer, Syed Arif Hussain, Haroonrashid M Hattiwale","doi":"10.1007/s12032-025-02988-8","DOIUrl":"10.1007/s12032-025-02988-8","url":null,"abstract":"<p><p>The global incidence of early-onset cancer has surged by nearly 80% over the past three decades, yet the underlying causes remain poorly understood. While genetics and lifestyle are among the traditional risk factors, emerging evidence implicates the human microbiome as a potent and overlooked contributor to early tumorigenesis. Increases in the studies that are exploring the tissue-specific microbiome signatures such as the enrichment of Actinomyces and Bacteroidia in early-onset colorectal cancer, or Enterobacter and Neisseria in pancreatic tumors offer compelling evidence for age-stratified microbial contributions. Additionally, the recent works on the establishment of gut-testis, oral-gut, and gut-liver microbial axes are being explored to understand the modulation of systemic immune and endocrine landscapes in younger individuals that might unravel their unique predisposition to malignancy. Further, the microbiome-cancer axis has been regarded as a hidden driver in the initiation and progression of early-onset malignancies across diverse tissue types. Understanding this link will provide the missing mechanistic insights showcasing how microbial dysbiosis, biofilm formation, and microbially derived metabolites promote oncogenic inflammation, DNA damage, and immune evasion contributing to early-onset cancers. Considering the potential of these studies, microbial biomarkers with diagnostic promises that include probiotics, fecal microbiota transplantation, and diet have also been explored as emerging tools for prevention and therapy. Through this study, we aim to understand early-onset cancer through a patient microbiota and underscore an urgent need to integrate microbial dynamics into cancer surveillance and intervention strategies, especially for young and largely asymptomatic populations.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"464"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006374","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":"Exploring the anticancer potential of R. tridentata extracts: a cytotoxicity study against human prostate cancer cell lines (LNCaP and DU145).","authors":"Ali Kudamba, Godfrey S Bbosa, Allan Lugaajju, Henry Wabinga, Nixon Niyonzima, Moses Ocan, Ali M Damani, Hussein M Kafeero, Jamilu E Ssenku, Shaban A Okurut, Muniiru Lubowa, Abdul Walusansa, S Sivagami Sivasundaram, Shobana Shampath, Haruna Muwonge","doi":"10.1007/s12032-025-02953-5","DOIUrl":"10.1007/s12032-025-02953-5","url":null,"abstract":"<p><p>This study investigates the cytotoxic effects of R. tridentata extracts on prostate cancer cells, providing insight into its potential therapeutic benefits and scientific validation for its traditional use in cancer treatment. The cytotoxicity of R. tridentata extracts was evaluated on prostate cancer cell lines (LNCaP and DU 145) using the MTT assay, with doxorubicin as a reference standard. Our findings demonstrated significant concentration- and time-dependent cytotoxic effects of the extracts on both cell lines (p < 0.0024 to p < 0.0002). Notably, the methanol extract exhibited potent cytotoxicity, with IC₅₀ values ranging from 124.07 to 211 μg/mL (DU145) and 100 to 180 μg/ml (LNCaP) over 24-72 h (p < 0.0024 to p < 0.0001), highlighting its therapeutic potential. This study unveils the promising cytotoxic activity of R. tridentata extracts, particularly methanol extracts, against prostate cancer cells, showcasing their concentration- and time-dependent effects. These findings underscore the potential of plant-derived extracts as therapeutic agents for cancer treatment, warranting further research.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"463"},"PeriodicalIF":3.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000916","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":"Diosgenin enhances the effect of radiation on head and neck cancer cells through apoptosis induction, G2/M cell cycle arrest, and ROS generation.","authors":"Mohadeseh Mohammadi, Fereshteh Koosha, Seyed Mohammad Amini, Fariborz Faeghi, Mikaeil Molazadeh, Hasan Goodarzi","doi":"10.1007/s12032-025-03019-2","DOIUrl":"10.1007/s12032-025-03019-2","url":null,"abstract":"<p><p>Radiotherapy is a cornerstone in treating head and neck cancers, yet its effectiveness is often limited by factors such as hypoxia and cancer stem cells. This study evaluated the radiosensitizing potential of diosgenin in KB cancer cells and normal HDF cells exposed to 4 Gy X-rays, with or without diosgenin. Cell viability, apoptosis, cell cycle distribution, ROS production, and expression of intrinsic apoptosis-related genes were assessed using MTT assays, flow cytometry, and RT-qPCR, respectively. Diosgenin alone reduced KB cell viability and, when combined with radiation (63 μM + 4 Gy), further decreased viability to 27.93 ± 1.8%, which was significantly lower than with either treatment alone (p < 0.05), while exhibiting lower toxicity in HDF cells. Diosgenin also induced G2/M arrest and amplified radiation-induced apoptosis, sub-G1 accumulation, and ROS production. These effects correlated with a marked increase in the Bax/Bcl-2 mRNA ratio in the combination group compared to either treatment alone (p < 0.0001), indicating activation of the intrinsic apoptotic pathway. Overall, the results suggest that diosgenin enhances the effect of radiation on head and neck cancer cells and may serve as a promising adjunct to radiotherapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"461"},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960384","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":"4D-printed microdevices for spatiotemporal detection of ctDNA and miRNA in pancreatic cancer: an in-depth review.","authors":"Noura A A Ebrahim, Thoraya A Farghaly, Soliman M A Soliman","doi":"10.1007/s12032-025-03021-8","DOIUrl":"10.1007/s12032-025-03021-8","url":null,"abstract":"<p><p>Pancreatic cancer is among the most lethal forms of cancer, with a five-year survival rate under 7%, primarily due to its late clinical presentation and rapid disease progression. Although the oncogenic development of pancreatic tumors can span over a decade, early diagnosis remains a major clinical challenge, as current diagnostic approaches-including imaging modalities and blood-based markers like CA19-9-lack the requisite sensitivity for detecting early-stage disease. Liquid biopsy has emerged as a promising, non-invasive diagnostic technique by enabling the detection of circulating tumor-specific nucleic acids, particularly circulating tumor DNA (ctDNA) and microRNAs (miRNAs). However, the practical use of these biomarkers is limited by their low concentrations in early disease stages, molecular fragility, and the demanding nature of current detection methods. The advent of 4D printing-a transformative advancement in additive manufacturing utilizing stimuli-responsive materials-has introduced novel opportunities for biomedical sensing. These responsive microdevices can undergo spatiotemporal changes, allowing for precise, time-regulated capture of molecular targets. This review presents a comprehensive analysis of 4D-printed micro- and nanodevices designed for ctDNA and miRNA detection, with an emphasis on their potential utility in pancreatic cancer diagnostics. We examine material selection, actuation strategies, fluid dynamics, device architecture, and emerging prototypes. Furthermore, the review considers clinical translation challenges, including regulatory pathways and integration into personalized medicine frameworks. In contrast to conventional PCR and NGS techniques-which, despite their high sensitivity, are often hindered by labor-intensive sample preparation, extended processing times, and reduced efficiency in identifying low-abundance biomarkers during the early stages of pancreatic cancer-4D-printed biosensors provide a dynamic, stimuli-responsive approach capable of enabling faster, more selective, and potentially point-of-care detection of ctDNA and miRNA. By combining smart material responsiveness with precise molecular capture mechanisms and compact device architectures, these platforms hold promise for addressing the sensitivity and stability challenges that limit traditional molecular diagnostic methods. Collectively, 4D-printed biosensors represent a promising frontier for advancing the early detection and real-time monitoring of pancreatic cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"462"},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992990","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":"Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.","authors":"Deepthi Maria Mathew, Abilash Valsala Gopalakrishnan","doi":"10.1007/s12032-025-03012-9","DOIUrl":"10.1007/s12032-025-03012-9","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal expansion of primitive hematopoietic stem cells. Despite therapeutic advances, including chemotherapy, hypomethylating agents, and FLT3 inhibitors, resistance and relapse remain major clinical challenges. One of the contributors to chemoresistance in AML is the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates redox homeostasis and promotes cell survival under oxidative stress. Under normal conditions, Kelch-like ECH-associated protein 1 (KEAP1) inhibits Nrf2. In response to oxidative stress, KEAP1 becomes inactivated, allowing Nrf2 to be activated. Nrf2 is then transported to the nucleus, where it facilitates the transcription of genes that protect cells from oxidative stress. Although vital for protecting cells from oxidative damage, recent studies have also proved the dual role of Nrf2 in cancer progression. The persistent activation of Nrf2 is associated with many cancer types, including AML. This review provides a brief discussion of the molecular mechanisms by which Nrf2 contributes to therapy resistance in AML, with a focus on its regulation of miRNAs, HO-1 1upregulation, and metabolic reprogramming via the pentose phosphate pathway (PPP). We also summarize the pathways involved in Nrf2 activation in AML and the limitations of current treatments that trigger oxidative stress, thereby leading to Nrf2-driven resistance. For AML treatment, recent research has placed a greater emphasis on combination therapy approaches that include Nrf2 inhibitors, in addition to traditional chemotherapeutic medicines such as doxorubicin, or targeted therapies like the BCL-2 inhibitor venetoclax. This review also analyses these studies to determine whether a combination strategy would be an appropriate method for treating AML.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"460"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960355","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 effect of U2AF1 mutation on erythroid differentiation and sensitivity to demethylation drug treatment.","authors":"Yuankai Liu, Xiu Li, Haitao Wang, Qiong Yang","doi":"10.1007/s12032-025-02956-2","DOIUrl":"10.1007/s12032-025-02956-2","url":null,"abstract":"<p><p>Myelodysplastic syndrome (MDS) is a group of blood disorders characterized by impaired maturation of erythroid cells. Mutations in the U2 small nuclear RNA auxiliary factor 1 (U2AF1) gene, particularly S34 (S34F/Y) and Q157 (Q157P/R), have been identified in 5-10% of MDS patients. By analyzing U2AF1 expression in hematopoietic stem progenitor cells and different blood cells in the GEO database, we have found the expression pattern of U2AF1 showed a significant stage specificity during normal erythropoiesis. To explore the specific impact of U2AF1 alterations on cellular function, we transduced K562 cells with lentivirus carrying four different types of U2AF1 mutants. Our results showed that these mutations significantly inhibited the growth of K562 cells. Mutations at the S34 sites (S34F and S34Y) reduced the mRNA expression levels of erythroid-related transcription factors GATA1, NF-E2, EKLF, and GFI-1B. The proportion of cells with CD71^lowCD235a^hig decreased, as well as the content of hemoglobin in K562 cells. In contrast, mutations at the Q157 site had opposite effects on these expression levels in K562 cells. Furthermore, we classified patients' risk ratings into three categories based on IPSS-R: moderate high-risk MDS, high-risk MDS, and very high-risk MDS. A total of 12 patients were analyzed, including 5 at moderate high-risk and 3 patients carrying mutations. Among 3 high-risk individuals, only one carried a mutation. 4 individuals at very high-risk, with 0 patients carrying the mutation. MDS patients with U2AF1 mutations (S34F, S34Y, Q157P, R156H) had significantly lower white blood cell, hemoglobin, and platelet counts than the MDS patients without these alterations. We hypothesize that treatment with Azacitidine (AZA) may lead to better recovery levels of hemoglobin and platelets for patients with U2AF1 mutations. Meanwhile, we found that U2AF1-mutated MDS patients have better responsiveness to demethylating drugs. We isolated and cultured peripheral blood mononuclear cells (PBMCs) carrying the U2AF1 S34F mutation from a high-risk MDS patient with a 7q chromosome deletion. The demethylating drug AZA could significantly inhibit their proliferation and induce apoptosis in the MDS PBMCs. In summary, our research demonstrated the following: (1) The effect of U2AF1 mutation on erythrocyte differentiation that S34 mutation inhibits the differentiation process, but the Q157 mutation promotes the differentiation process. (2) The level of erythrocyte changes in U2AF1-mutated MDS patients should receive more attention. (3) It also showed that demethylating drugs have promising therapeutic effects in treating MDS patients carrying U2AF1 mutations.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"459"},"PeriodicalIF":3.5,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960463","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}