Frontiers in Cell and Developmental Biology最新文献

{"title":"Intelligent segmentation of thyroid nodule ultrasound images based on benign-malignant-aware semantic prototype calibration and class-conditional boundary refinement.","authors":"Bin Luo, Runwen Li, Yao Tang","doi":"10.3389/fcell.2026.1879094","DOIUrl":"https://doi.org/10.3389/fcell.2026.1879094","url":null,"abstract":"<p><strong>Introduction: </strong>Ultrasound-based thyroid nodule segmentation remains challenging because of blurred boundaries, complex echo noise, and subtle morphological differences between benign and malignant lesions.</p><p><strong>Methods: </strong>We propose a benign-malignant-aware segmentation framework based on SegFormer, incorporating adaptive semantic prototype calibration (ASPC) for class-level semantic discrimination and class-conditional boundary refinement (CCBR) for ambiguous contour correction. The model performs three-class segmentation of background, benign, and malignant regions.</p><p><strong>Results: </strong>Experiments on the public TN3K dataset and an in-house clinical dataset demonstrate consistent performance under both external transfer and supervised evaluation settings. The proposed method achieved PA, mIoU, mDice, and mPrecision of 0.9449, 0.6427, 0.7517, and 0.8147 on TN3K; 0.7793, 0.5016, 0.6374, and 0.7089 under direct external transfer; and 0.8521, 0.6124, 0.7328, and 0.7996 under supervised in-house evaluation.</p><p><strong>Discussion: </strong>Ablation studies and Grad-CAM visualization further confirm that ASPC and CCBR improve semantic discrimination, boundary refinement, and model interpretability, supporting the effectiveness of the proposed framework for thyroid nodule segmentation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1879094"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule regulation in cancer cells.","authors":"Alexandre Matov","doi":"10.3389/fcell.2025.1677302","DOIUrl":"https://doi.org/10.3389/fcell.2025.1677302","url":null,"abstract":"<p><strong>Introduction: </strong>The notion of microtubule (MT) dynamics relates to the changes in the length of MT polymers in living cells. They are governed by a stochastic process related to the rates and chances of adding or removing tubulin dimers at the ends of MT polymers, termed dynamic instability. The ability of each MT to swiftly switch between stages of adding or removing dimers at the tip of its lattice is critical for the overall success of the mitotic spindle, a molecular machinery built dynamically by MTs and associated molecular motor proteins, in properly segregating the duplicated DNA into the two daughter cells. When changes in the genetic and epigenetic regulation of the cell affect this ability, for example, by increasing the rates of hydrolysis of bound to tubulin dimers incorporated in the MT lattice, that results in segregation errors and is a hallmark of disease.</p><p><strong>Methods: </strong>In cancer, the dysregulation of MT dynamics contributes to drug resistance. Measuring and modeling MT dynamics provides an insight into the regulation of the cell and its susceptibility to drug action. It can also characterize the function of patient immune cells and contribute to improving the success rate of cell therapy.</p><p><strong>Results: </strong>Our investigation indicates that drug-resistant tumors exhibit particular changes in their regulation at the cellular level that expose cell state vulnerabilities, which can be targeted during therapy. We elucidate mechanisms of oncogenic activity in dividing cells and propose an approach for overcoming drug resistance.</p><p><strong>Conclusion: </strong>Changes in MT regulation before and after drug treatment of patient cells are indicative of the susceptibility of tumors to particular drug regimens.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1677302"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of molecular profiling for castration-resistant prostate cancer treatment and therapy development.","authors":"Timothy J Mann, Therese M Becker, Tara L Roberts, Paul de Souza, John G Lock","doi":"10.3389/fcell.2026.1894354","DOIUrl":"https://doi.org/10.3389/fcell.2026.1894354","url":null,"abstract":"<p><p>Early-stage prostate cancer (PCa) is overwhelmingly driven by aberrant androgen receptor (AR) signalling. Accordingly, standard-of-care treatments include androgen deprivation therapy (ADT) and AR pathway inhibitors (ARPIs), with disease detection and therapy-response monitoring relying on blood-borne PSA, a product of AR transcriptional programs. Crucially, resistance to these therapies is inevitable but heterogeneous in nature; potentially driven by a diverse array of alternate signalling pathways and differentiation mechanisms such as neuroendocrine conversion. Here, we review the current standard of care for CRPC and highlight this heterogeneity - between and even within patients - which demands a new paradigm to longitudinally monitor the evolving molecular profiles of each patient to guide rational selection of targeted therapies, as well as rational patient stratification to optimise clinical trials for emerging therapies. Since solid biopsies are incompatible with extensive longitudinal profiling, we here consider recent advances in liquid biopsy-based profiling methods and assess their potential as cornerstones in a new paradigm of personalised, adaptable disease monitoring and therapeutic decision-support.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1894354"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes-nano-messengers in tumors: capturing techniques, birth codes, and functional deciphering.","authors":"Ying-Ying Li, Ya Gao, Yan-Hong Wang, Kai-Fang Zhou, Yang Zhao, Li-Juan Zhao","doi":"10.3389/fcell.2026.1825151","DOIUrl":"https://doi.org/10.3389/fcell.2026.1825151","url":null,"abstract":"<p><p>Exosomes are nanoscale, membrane-bound vesicles secreted by various cell types. Owing to their cargo of parental cel-derived cellular components, exosomes show significant promise as clinical biomarkers. Meanwhile, due to their diverse origins and cargo, exosomes play a dual role in cancer, possessing the capacity to both promote and suppress tumor progression The efficient and rapid isolation and purification of exosomes are foundational for advancing their clinical applications. Additionally, a comprehensive understanding of exosome biogenesis is essential to elucidate their underlying biological functions. However, current knowledge regarding their biological characteristics and functions of action remains limited. This review delves into exosome isolation techniques, the regulatory mechanisms underlying their biogenesis and secretion, and their dual roles in cancer progression, metastasis, and tumor immunity, concluding with a discussion of the challenges and future directions in their clinical translation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1825151"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral and upper gastrointestinal Crohn's disease: new perspectives on pathogenesis and clinical management.","authors":"Xianhong Shi, Beibei Wang, Xiaohui Zhao, Heng Li, Tianqi Zhou, Bin Li, Lulu Tian, Kai Yin","doi":"10.3389/fcell.2026.1907519","DOIUrl":"https://doi.org/10.3389/fcell.2026.1907519","url":null,"abstract":"<p><p>Crohn's disease is a chronic inflammatory bowel disease that is closely associated with genetic factors, immune dysregulation and microbial imbalance. Lesions involving the oral cavity and upper gastrointestinal tract constitute a common yet clinically overlooked manifestation of this disease. This article reviews the cellular and molecular mechanisms underlying disease onset and progression, and evaluates the diagnostic performance of various noninvasive and serum biomarkers. It also summarizes multimodal diagnostic approaches and corresponding therapeutic strategies based on current clinical practice. Currently, relevant clinical trials and standardized evaluation criteria remain lacking, largely because of the limited understanding of disease pathogenesis. Therefore, high-quality basic and translational research will be essential to deepen the understanding of this disease and facilitate the development of precision diagnostic and therapeutic strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1907519"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and internal validation of a task-conditioned multimodal radiology-pathology model for breast cancer staging and biomarker profiling: a retrospective cohort study.","authors":"Yang Liu, Yunfei Dong, Guiyun Zhang, Yue Wu, Shanshan Zhang, Yufo Chen, Ruirui Cao, Rui Wang, Chengliang Yin, Yumei Li","doi":"10.3389/fcell.2026.1863777","DOIUrl":"https://doi.org/10.3389/fcell.2026.1863777","url":null,"abstract":"<p><strong>Objectives: </strong>To retrospectively develop and evaluate a task-conditioned multimodal artificial intelligence framework, in which a learned task embedding and modality-availability mask generate endpoint-specific weights over predefined radiology-only, pathology-only, and fusion experts, for breast cancer staging and biomarker profiling.</p><p><strong>Methods: </strong>We retrospectively assembled a cohort of 923 patients with paired radiology and pathology data. Nine tasks included TNM components [tumor extent (T), nodal involvement (N), and distant metastasis (M)], clinical stage, histological grade, and estrogen receptor, progesterone receptor, HER2, and Ki-67 status. Five convolutional neural network backbones were benchmarked for each modality. Task-specific models were selected by validation AUROC, and a late-fusion transformer was used for paired data. We further evaluated learned MoE gating, task-conditioned MoE routing with task embeddings and modality-availability masks, missing-modality robustness, and paired-bootstrap AUROC comparisons. An independent external cohort assessed feasibility for mammography-based pathological complete response and pathology-based triple-negative breast cancer (TNBC) prediction.</p><p><strong>Results: </strong>Best single-modality models achieved AUROCs ranging from 0.606 to 0.990 across tasks, with an AUROC of 0.990 observed for M staging and strong performance observed for histological grade (AUROC, 0.949; accuracy, 0.908) and HER2 status (AUROC, 0.810; accuracy, 0.762). Fixed late fusion improved the mean AUROC from 0.813 to 0.826. Learned MoE gating and task-conditioned MoE further improved mean AUROC to 0.830 and 0.834, respectively. Task-conditioned MoE improved mean AUROC by 0.009 over fixed late fusion (95% CI, 0.005-0.013; P = 0.011) and by 0.021 over the best single-modality expert. Under 70% random missing-modality simulation, task-conditioned MoE outperformed fixed fusion with zero imputation by 0.067 mean AUROC. In external feasibility analyses, the mammography-based pCR model achieved an AUROC of 0.758, and the pathology-based triple-negative breast cancer model achieved an AUROC of 0.872.</p><p><strong>Conclusion: </strong>OmniBreast demonstrated the feasibility of task-conditioned radiology-only, pathology-only, and fused prediction in the internal nine-task benchmark. The external analyses provided preliminary support for feasibility on two related endpoint-extension tasks but did not establish generalizability across the nine primary tasks; multicenter external validation and prospective clinical evaluation remain necessary.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1863777"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An isogenic hiPSC-derived keratinocyte model reveals CXCL10/CXCL11 inflammatory dysregulation in epidermolysis bullosa simplex.","authors":"Manoubia Saidani, Sabrina Martineau, Marwa Mahmoud, Sophie Domingues, Manon Doyen, Lina El Kassar, Smail Hadj-Rabia, Christine Bodemer, Jennifer Allouche, Christine Baldeschi, Nathalie Holic","doi":"10.3389/fcell.2026.1918694","DOIUrl":"https://doi.org/10.3389/fcell.2026.1918694","url":null,"abstract":"<p><p>Epidermolysis bullosa simplex (EBS) is a genetic skin disorder driven by dominant pathogenic variants in <i>KRT5</i> or <i>KRT14</i> genes, leading to cytoskeletal fragility in basal keratinocytes and intraepidermal blistering. No curative therapies are currently available, and the link between keratin mutations and disease mechanisms remains incompletely understood. To further investigate the inflammatory component of EBS, we used a model of hiPSC-derived keratinocytes carrying dominant <i>KRT5</i> variants, alongside a genetically corrected isogenic counterpart. This approach established a direct link between the <i>KRT5</i> variants and keratin aggregation, impaired proliferation, and an inflammatory phenotype. The inflammatory signature was confirmed by increased expression of IL1A and IL1B, consistent with previous observations in EBS, while CXCL10 and CXCL11 emerged as newly identified dysregulated chemokines. Their consistent increase across independent cell lines, elevated secretion, and normalization in the CRISPR-corrected isogenic cells indicate that <i>KRT5</i> variants trigger a keratinocyte-intrinsic CXCL10/CXCL11 inflammatory response. Pharmacological inhibition of the IFN-γ-JAK1/2-STAT1 pathway suppressed their secretion, supporting JAK inhibition as a potential therapeutic strategy to modulate EBS-associated inflammatory dysregulation. In conclusion, this study shows that beyond structural defects, <i>KRT5</i> variants establish a keratinocyte-intrinsic inflammatory phenotype in which the CXCL10 and CXCL11 axis emerges as a key disease-associated signature and a promising therapeutic target.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918694"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.","authors":"Xiaojie Chen, Weidong Wang, Fangxin Shen, Zhiwei Zhao","doi":"10.3389/fcell.2026.1840428","DOIUrl":"https://doi.org/10.3389/fcell.2026.1840428","url":null,"abstract":"<p><p>Mitochondrial ribosomes (mitoribosomes), particularly mitochondrial ribosomal subunit proteins (MRPS), are emerging as contributors to cancer metabolic reprogramming. Rather than static components of mitochondrial translation, MRPS exhibit pronounced spatiotemporal heterogeneity that shapes tumor metabolic plasticity and therapeutic response. This review systematically summarizes evidence that MRPS functions are dynamically regulated across tumor progression and spatial microenvironments. Temporally, MRPS mediate metabolic switching between oxidative phosphorylation (OXPHOS) and glycolysis, contributing to metabolic adaptation, treatment resistance, and tumor evolution. Spatially, MRPS display context-dependent functions across tumor regions, cancer types, and metabolic microenvironments, thereby contributing to intratumoral metabolic diversity. We further highlight that MRPS-associated metabolic plasticity is linked with lactate metabolism and hypoxia-inducible factor (HIF) signaling, forming feedback networks associated with tumor growth, immune escape, and therapy resistance. This spatiotemporal regulatory axis challenges the traditional static view of mitochondrial dysfunction in cancer. Targeting MRPS-associated metabolic adaptation may provide therapeutic opportunities beyond the traditional Warburg framework. Emerging technologies, including lactate-sensitive nanoprobes, reactive oxygen species (ROS)-responsive delivery systems, and MRPS-related imaging platforms, may support metabolic monitoring and targeted therapeutic intervention. Collectively, this framework links mitochondrial translation with tumor metabolism and microenvironmental regulation, providing additional insight into metabolic adaptation in cancer.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1840428"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified frailty index predicts programmed cell death activation and sepsis risk after total hip arthroplasty: a retrospective cohort study.","authors":"Yue Wei, Sai Xu, Minjie Yang","doi":"10.3389/fcell.2026.1888879","DOIUrl":"https://doi.org/10.3389/fcell.2026.1888879","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the relationship between mFI-defined frailty and the activation of programmed cell death (PCD) pathways-apoptosis, pyroptosis, necroptosis, and ferroptosis-in elderly patients who developed infection-related sepsis after total hip arthroplasty (THA), and to evaluate whether integrating mFI with circulating cell death biomarkers improves prognostic stratification of post-THA sepsis severity and clinical trajectory. The original framing of the combined model as a \"predictive\" tool was revised: the combined biomarker model now describes the ability to stratify severity and clinical trajectory once sepsis is diagnosed, not to predict its occurrence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective cohort study was conducted on 188 elderly patients (≥65 years) who underwent primary THA between January 2020 and January 2024. Frailty was assessed using the mFI-11 tool. All patients were monitored for postoperative infection-related sepsis (Sepsis-3 criteria) within 30 days. In patients who developed sepsis (n = 30), circulating biomarkers of pyroptosis (gasdermin D, NLRP3, caspase-1), necroptosis (RIPK3), ferroptosis (GPX4, 4-HNE), apoptosis (caspase-3), and DAMPs (HMGB1, cell-free DNA) were measured at 48 h post-onset. Multivariate logistic regression, multiple linear regression, and ROC curve analyses were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Post-THA sepsis occurred in 30 patients (16.0%), with incidence increasing across frailty strata: non-frail 3.3%, mild frailty 14.9%, moderate-to-severe frailty 29.7% (P = 0.006). mFI score was an independent predictor of post-THA sepsis (OR = 1.52, 95% CI: 1.28-1.81, P &lt; 0.001). Patients with sepsis exhibited markedly elevated gasdermin D (386.4 ± 128.6 vs. 42.8 ± 18.4 pg/mL), RIPK3 (52.4 ± 21.8 vs. 6.4 ± 2.8 ng/mL), HMGB1 (62.4 ± 24.8 vs. 8.4 ± 3.6 ng/mL), and depleted GPX4 (8.6 ± 3.4 vs. 34.2 ± 10.6 ng/mL) compared with non-sepsis THA patients (all P &lt; 0.001). Within the sepsis cohort, mFI positively correlated with gasdermin D (r = 0.74), RIPK3 (r = 0.71), and HMGB1 (r = 0.78), and inversely with GPX4 (r = -0.72; all P &lt; 0.001). A combined model integrating mFI with HMGB1, gasdermin D, and GPX4 achieved AUC = 0.904 for stratifying sepsis severity and clinical trajectory once diagnosis is established, superior to mFI alone (AUC = 0.742; DeLong P &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Frailty, as quantified by mFI, is strongly associated with the concurrent activation of pyroptosis, necroptosis, and ferroptosis pathways in post-THA infection-related sepsis. Integrating mFI with DAMP and cell death biomarkers substantially improves prognostic stratification of sepsis severity and clinical trajectory once diagnosis is established, supporting the clinical utility of frailty-guided perioperative cell death monitoring. A preoperative prediction model based on mFI, haemoglobin, and ASA class provides clinically accessible risk stratification, warranting prospec","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1888879"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coagulation activation is associated with genomic-instability-related features in TP53-mutated AML and MDS: routine laboratory patterns beyond classical disseminated intravascular coagulation.","authors":"Xiaoqin Xin, Chaoqiang Zheng, Jungao Huang, Qing Xie","doi":"10.3389/fcell.2026.1918027","DOIUrl":"https://doi.org/10.3389/fcell.2026.1918027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Disseminated intravascular coagulation (DIC) is a serious complication of acute myeloid leukemia (AML) associated with poor prognosis. In TP53-mutated AML and myelodysplastic syndrome (MDS), however, the classical ISTH criteria rarely identify overt DIC, although bleeding and thrombotic complications are well documented in acute leukaemia. We hypothesized that these patients exhibit a lower-grade, subclinical coagulation activation that is associated with the underlying genomic-instability-related features of TP53-mutant disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively analyzed 107 consecutive patients with TP53-mutated AML (n = 52) or high-risk MDS (MDS, n = 55), median age 65 years, diagnosed and initially evaluated at our centre between 2018 and 2025. Seven routine coagulation markers and 46 co-mutated genes were evaluated for associations with overall survival (OS) using univariate and multivariable Cox regression, continuous dose-response modeling, and unsupervised k-means clustering. Internal validity was assessed by 1000 bootstrap resamples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overt DIC according to ISTH criteria was rare (15%). Subclinical activation was common: 50% of patients had a D-dimer ≥1 μg/mL, 41% a fibrinogen ≥4 g/L, and 29% an INR ≥1.2. In univariate analysis, D-dimer, fibrinogen, INR, prothrombin time, and activated partial thromboplastin time were each associated with OS (HR 1.33-1.38 per SD; all p &lt; 0.05). Complex karyotype correlated with higher D-dimer (median 1.39 vs. 0.60 μg/mL, p = 0.022) and fibrinogen (3.91 vs. 2.53 g/L, p = 0.007), while TP53 variant allele frequency (VAF) showed modest positive correlations with D-dimer (ρ = 0.21), INR (ρ = 0.27), and PT (ρ = 0.27; all p &lt; 0.05). Clustering identified three coagulation phenotypes: Silent (51%), Thrombo-inflammatory (31%), and Consumption-like (18%), showing a graded but statistically non-significant gradient in molecular features and a stepwise decline in median OS (14, 10 and 8 months; log-rank p = 0.041). After adjustment for complex karyotype, TP53 VAF, and favorable co-mutation count, the Consumption-like phenotype was associated with a non-significant increased risk (HR 1.83, 95% CI 0.92-3.65, p = 0.084), whereas favorable co-mutation pathways remained independently protective (HR 0.56, 95% CI 0.35-0.90, p = 0.016).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In TP53-mutated AML/MDS, coagulation activation intensity is associated with the degree of genomic instability. The three phenotypes may add biological resolution beyond classical DIC and cytogenetic risk groups, but represent laboratory patterns rather than validated bleeding or thrombosis prediction tools. However, after accounting for genomic features, phenotypes were not independent predictors of outcome, with complex karyotype, TP53 VAF, and favorable co-mutation count driving prognosis. Because treatment intensity and other clinical confounders were not available, these s","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918027"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}