FEBS Open BioPub Date : 2026-08-26DOI: 10.1002/2211-5463.70326
Alexander Wlodawer, Pawel Rubach, Zbigniew Dauter, Wojciech Dec, Dariusz Brzezinski, Marta Kulik, Wladek Minor, Mariusz Jaskolski
{"title":"Comparative assessment of crystallographic and cryo-EM models in the Protein Data Bank.","authors":"Alexander Wlodawer, Pawel Rubach, Zbigniew Dauter, Wojciech Dec, Dariusz Brzezinski, Marta Kulik, Wladek Minor, Mariusz Jaskolski","doi":"10.1002/2211-5463.70326","DOIUrl":"10.1002/2211-5463.70326","url":null,"abstract":"<p><p>With cryogenic electron microscopy (cryo-EM) on track to surpass X-ray crystallography as the preferred method for determining macromolecular structures, it is important to evaluate and compare the quality of structure models obtained by these methods. This allows us to assess whether the rapidly growing numbers (quantity) correlate with quality and to identify areas in which each method excels or falls short. Selected quality-related parameters were compared for 97 200 crystal structures and 30 139 cryo-EM structures released by the Protein Data Bank (PDB) between 2015 and 2025. Comparison of geometric and stereochemical parameters indicated that, despite significant differences in the resolution of the experimental data, these values were, in the vast majority of cases, close to the expected targets. Nevertheless, we found that crystal structures tend to exhibit more Ramachandran and rotamer outliers than cryo-EM structures, although they unexpectedly have lower clashscore values. Separately, we compared the quality of 612 crystal and 1817 cryo-EM structures in the PDB representing complete ribosomes or their subunits. For this subset of very large, well-defined macromolecules, we found that the quality of many cryo-EM models is higher than that of their crystal counterparts, and that the best cryo-EM structures were also determined at higher resolution. Overall, we conclude that the availability of both techniques has clearly resulted in major advances during the last decade and bodes very well for the future.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-26DOI: 10.1002/2211-5463.70329
Maria C Zabala-Rodriguez, Juliette K Tinker, Teresa Frisan, Taj Azarian, Ken Teter
{"title":"Salmonella enterica serovar typhi limits the potency of typhoid toxin and ADP-ribosylating toxin AB to establish a persistent infection.","authors":"Maria C Zabala-Rodriguez, Juliette K Tinker, Teresa Frisan, Taj Azarian, Ken Teter","doi":"10.1002/2211-5463.70329","DOIUrl":"10.1002/2211-5463.70329","url":null,"abstract":"<p><p>Chronic infection is important for the transmission of Salmonella enterica serovar Typhi (S. Typhi), an obligate human pathogen responsible for typhoid fever. The immunomodulatory action of typhoid toxin helps establish an initial stealth invasion of the intestinal tract that can lead to systemic spread, colonization of the gallbladder, and persistent shedding. Typhoid toxin contains a cell-binding pentamer and two catalytic subunits: cytolethal distending toxin B (CdtB, a DNase) and pertussis-like toxin A (PltA, an ADP-ribosyltransferase). It undergoes endocytosis and transport to the endoplasmic reticulum (ER) where toxin disassembly occurs. This allows the catalytic subunits to exit the ER for interaction with their nuclear or cytosolic targets. However, all known cellular and physiological effects of typhoid toxin are attributed to CdtB. These effects reduce the severity of intestinal inflammation, promoting host survival and long-term infections. PltA has in vitro enzymatic activity but does not affect cells challenged with typhoid toxin. It is thought that the cytosolic action of PltA will be identified in future work. We instead propose that PltA never reaches the cytosol: it is retained in the ER to limit toxin potency, thereby allowing the anti-inflammatory effects of CdtB to promote intestinal colonization. The absence of Salmonella ADP-ribosylating toxin AB (ArtAB) from all strains of S. Typhi may serve a similar purpose. We accordingly propose a model of balanced pathogenicity in which the lack of toxin ADP-ribosyltransferase activity is essential for S. Typhi pathogenesis.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-23DOI: 10.1002/2211-5463.70333
Yingying Chen, Hui Li
{"title":"BCG vaccination potentiates oxidative phosphorylation in neonatal myeloid-derived suppressor cells.","authors":"Yingying Chen, Hui Li","doi":"10.1002/2211-5463.70333","DOIUrl":"10.1002/2211-5463.70333","url":null,"abstract":"<p><p>Bacillus Calmette-Guérin (BCG) vaccination has well-documented off-target effects in early life, but the underlying molecular mechanisms remain incompletely understood. This study investigated whether BCG reprograms neonatal myeloid-derived suppressor cells (MDSCs) through oxidative phosphorylation (OXPHOS). After neonatal mice received a subcutaneous injection of BCG or PBS, the effects of BCG exposure on splenic monocytic (M-) and polymorphonuclear (PMN-) MDSCs were assessed. BCG vaccination significantly increased the expression of OXPHOS-related genes (Ndufab1, Sdhd, Uqcrfs1, Cox4i) and mitochondrial oxidative activity in both MDSC subsets. Seahorse analysis revealed a higher oxygen consumption rate in BCG-exposed PMN-MDSCs. Functional assays showed that BCG impaired MDSC-mediated T-cell suppression, with oligomycin treatment partially able to restore this suppressive capacity. Together, these findings indicate that BCG-induced OXPHOS potentiation contributes to the loss of MDSC immunosuppressive function in neonatal mice, providing a molecular mechanism for the non-specific immunomodulatory effects of BCG vaccination early in life.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-21DOI: 10.1002/2211-5463.70327
Alejandro Delgado-Rey, Miriam Livier Llamas-García, Gabriela M Montero-Morán, Leticia Santos, Samuel Lara-González
{"title":"Structural and biochemical insights into the thermostable esterase Ta0887 from Thermoplasma acidophilum.","authors":"Alejandro Delgado-Rey, Miriam Livier Llamas-García, Gabriela M Montero-Morán, Leticia Santos, Samuel Lara-González","doi":"10.1002/2211-5463.70327","DOIUrl":"10.1002/2211-5463.70327","url":null,"abstract":"<p><p>Microbial esterases are versatile and stable enzymes with a wide range of biotechnological applications. However, few esterases have been characterized from archaea, an important source of extremophilic enzymes. In this study, we report the biochemical characterization and crystal structure of Ta0887, a novel esterase from the thermoacidophilic archaeon Thermoplasma acidophilum. The protein was successfully cloned, expressed, and purified in Escherichia coli. Light scattering assays revealed that Ta0887 is a monomer in solution. Activity assays using p-nitrophenyl (p-NP) esters confirmed its esterase activity, showing a substrate preference for p-NP hexanoate (C6). Furthermore, the substitution of Ser95 with alanine completely abolished enzymatic activity, thereby confirming its essential role as the nucleophilic residue of the catalytic triad. The enzyme exhibited optimal activity at 65 °C and pH 8.0. Notably, Ta0887 displayed high thermal stability, retaining 66% residual activity after incubation at 80 °C for 2 h, consistent with its thermal denaturation midpoint temperature of 80.6 °C. The crystal structure of Ta0887, resolved at 1.93 Å, revealed an α/β-hydrolase core domain consisting of an eight-strand β-sheet, surrounded by seven α-helices, and a cap domain comprising four α-helices. Ta0887 features a large substrate-binding pocket at the interface between the two domains that contains the conserved residues Ser95, Asp187, and His215 of the catalytic triad. Further analysis indicates that an efficiently packed hydrophobic core is a key feature for the observed thermostability. The findings from this study provide a basis for the future engineering of Ta0887 with the aim of enhancing its potential for industrial and biotechnological applications.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-20DOI: 10.1002/2211-5463.70318
Jenica H Kakadia, Rachel Heilmann, Maximiliano Barrientos, Laura MacNeill, Ingrid Vallee, Sarah K Schultz, Patrick O'Donoghue, Angelica A Moresco, Victoria M Siu, Ilka U Heinemann
{"title":"From patient advocacy to patient-driven research: Building active partnerships beginning at the bench to reach the bedside.","authors":"Jenica H Kakadia, Rachel Heilmann, Maximiliano Barrientos, Laura MacNeill, Ingrid Vallee, Sarah K Schultz, Patrick O'Donoghue, Angelica A Moresco, Victoria M Siu, Ilka U Heinemann","doi":"10.1002/2211-5463.70318","DOIUrl":"https://doi.org/10.1002/2211-5463.70318","url":null,"abstract":"<p><p>Patient advocates offer lived experience that can shape research priorities, methods, and outcomes. Patient engagement contributes valuable resources to research, including meaningful additions to research design, definition of research priorities, and dissemination of outcomes. It is therefore critical that patients and patient advocates be part of the biomedical research process; which can be achieved by changing the perspective of patients as the recipients of research outcomes, to being partners in the process. Patient, clinician, and researcher interactions are particularly important in rare disease research, where little funding is allocated to each disease, making the definition of research priorities even more important. Here, we outline how patients can contribute to biomedical research and provide a step-by-step guide for patient engagement at scientific conferences.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-19DOI: 10.1002/2211-5463.70330
John Allan, Amias Alstrom-Moore, Gary W Black
{"title":"A minimal cellulosome-like system in Cellulosilyticum lentocellum.","authors":"John Allan, Amias Alstrom-Moore, Gary W Black","doi":"10.1002/2211-5463.70330","DOIUrl":"https://doi.org/10.1002/2211-5463.70330","url":null,"abstract":"<p><p>Cellulosomes are efficient enzymatic nanomachines which have arisen for the degradation of cellulosic biomass. They are found abundantly in soil-dwelling microbes and bacteria which thrive in the stomachs of ruminant mammals. Two protein domains, cohesins and dockerins, characterise cellulosomes. These domains interact with each other to form, in many cases, enormous complexes with as many as 160 individual proteins. However, genome annotation of Cellulosilyticum lentocellum DSM 5427 revealed a single cohesin domain (encoded by Clole_2599) and a single dockerin domain (Clole_2598). Therefore, we recombinantly expressed ClcC and ClcD and found they form a (predicted ~ 104 kDa) heterodimeric complex. We show that this complex formation enhances cellulase activity approximately 2-fold on insoluble microcrystalline cellulose and 1.25-fold on soluble carboxymethyl cellulose. Moreover, we identified two additional candidate interacting partners for ClcC, one of which appears to bind via a non-canonical interface. These findings suggest that cellulosomal principles can operate in highly reduced cohesin-dockerin systems.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-19DOI: 10.1002/2211-5463.70328
Takashi Kato, Suzu Tanaka, Miyu Ohashi
{"title":"Threonine 348 regulates the subcellular localization of PTEN.","authors":"Takashi Kato, Suzu Tanaka, Miyu Ohashi","doi":"10.1002/2211-5463.70328","DOIUrl":"https://doi.org/10.1002/2211-5463.70328","url":null,"abstract":"<p><p>The tumor suppressor PTEN (phosphatase and tensin homolog) dephosphorylates PIP<sub>3</sub> (phosphatidylinositol (3,4,5)-trisphosphate) at the plasma membrane and protects genomic integrity in the nucleus; thus, regulation of PTEN subcellular localization is crucial. Previous studies have shown that the PTEN<sub>350</sub> fragment is markedly enriched in the nucleus, a feature not explained by the N-terminal nuclear localization signal. In this study, we generated PTEN fragments of various lengths and identified PTEN<sub>348</sub> (residues 1-348), which showed prominent nuclear localization. Furthermore, the replacement of threonine 348 (Thr348) with other amino acids reduced the nuclear localization of the PTEN<sub>348</sub> and PTEN<sub>350</sub> fragments. Moreover, we found that PTEN<sub>A4</sub> and PTEN<sub>K13R,A4</sub> localized predominantly to the nucleus and plasma membrane, respectively, and that substitution of Thr348 with aspartic acid resulted in cytoplasmic localization in both mutants. Collectively, these results indicate that Thr348 is a key contributor to the regulation of PTEN subcellular localization.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-13DOI: 10.1002/2211-5463.70321
Nicolas Germain, Elise Buret, Le Hoang Thanh Nguyen, Marion Cocheteux, Nicolas Touya, Mélanie Dhayer, Romain Dubois, Frank Lafont, Sebastien Janel, Patrice Maboudou, Steve Lancel, Philippe Marchetti
{"title":"GelMA-based 3D spheroids recapitulate transcriptomic and functional hallmarks of myeloid sarcoma.","authors":"Nicolas Germain, Elise Buret, Le Hoang Thanh Nguyen, Marion Cocheteux, Nicolas Touya, Mélanie Dhayer, Romain Dubois, Frank Lafont, Sebastien Janel, Patrice Maboudou, Steve Lancel, Philippe Marchetti","doi":"10.1002/2211-5463.70321","DOIUrl":"10.1002/2211-5463.70321","url":null,"abstract":"<p><p>Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myeloid leukemia (AML). Conventional two-dimensional cultures fail to replicate the constraints of the MS microenvironment. We demonstrated that 5% gelatin methacrylate (GelMA) hydrogels provide a tunable three-dimensional matrix for in vitro modeling of MS. GelMA hydrogels exhibited tissue-like stiffness and oxygen diffusion properties, supporting the formation of viable spheroids from myeloid leukemia cell lines. The 3D context induced G1 cell cycle arrest and apoptotic progression, reflecting dormancy at extramedullary sites. RNA sequencing revealed transcriptional reprogramming in GelMA-embedded spheroids, with an enrichment in ECM remodeling and metabolic pathways. Furthermore, transcriptomic profiles from 3D-cultured cells aligned with patient-derived MS samples, validating the model's relevance to MS. Thus, we present a GelMA-based system which provides a clinically relevant platform for investigating MS biology and screening potential therapeutic strategies.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-13DOI: 10.1002/2211-5463.70322
Pragya Gupta, Sebastian Gb Furness, Tahereh Gharbi, Ric De Paoli-Iseppi, Shweta S Joshi, Michael Clark, David L Hare, Peter Wookey
{"title":"Identification and characterisation of calcitonin receptor isoforms expressed in glioblastoma derived glioma stem and U-87 MG cells.","authors":"Pragya Gupta, Sebastian Gb Furness, Tahereh Gharbi, Ric De Paoli-Iseppi, Shweta S Joshi, Michael Clark, David L Hare, Peter Wookey","doi":"10.1002/2211-5463.70322","DOIUrl":"10.1002/2211-5463.70322","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly lethal brain cancer in which the calcitonin receptor (CT Receptor), encoded by the CALCR gene, is expressed in 78-88% of patient biopsies. Here, we investigate whether the CT Receptor plays a role in cancer cell survival. In cancer cell lines, knockdown of CALCR disrupts the cell cycle and induces apoptosis, supporting an essential pro-survival role. The CALCR gene produces three main transcripts in humans, of which Transcript 1 encodes CALCR<sub>b</sub> mRNA including exon 10 and is translated into the CT<sub>b</sub> Receptor isoform, and Transcripts 2 and 3 which are translated into the CT<sub>a</sub> Receptor. CALCR<sub>b</sub> expression is conserved across a diverse range of mammalian species. We examined the expression of all CT Receptor isoforms (CALCR<sub>total</sub>) and CALCR<sub>b</sub> expression in four high-grade glioma stem-like cell lines and in U-87 MG glioblastoma cells. Using qPCR, we observed stable levels of both CALCR<sub>total</sub> and CALCR<sub>b</sub> expression under conditions of autophagy or apoptosis, consistent with a requirement for CALCR<sub>b</sub> in cell survival. As alternative splicing (AS) of key genes in cancers confers tumour resilience, we investigated AS of CALCR transcript 2 using long-read nanopore sequencing. Unexpectedly, we discovered a novel AS event causing inclusion of exon 10 within Transcript 2 in all glioblastoma cell lines investigated. This finding, together with stable CALCR<sub>b</sub> expression under cellular stress and the finding by other groups confirming that knockdown of CT Receptor compromises cell survival, implicates the CT<sub>b</sub> Receptor as a potential oncoprotein.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2026-08-13DOI: 10.1002/2211-5463.70323
Adam Albitar, Sally Agersborg, Ahmed Charifa, Pooja Phull, Noa Biran, David Vesole, Harsh Parmar, Andrew Pecora, Andrew Ip, Andre Goy, David Siegel, Maher Albitar
{"title":"Using cell-free RNA to identify B- and T-cell clonality for diagnosis and monitoring of B- and T-cell neoplasms.","authors":"Adam Albitar, Sally Agersborg, Ahmed Charifa, Pooja Phull, Noa Biran, David Vesole, Harsh Parmar, Andrew Pecora, Andrew Ip, Andre Goy, David Siegel, Maher Albitar","doi":"10.1002/2211-5463.70323","DOIUrl":"10.1002/2211-5463.70323","url":null,"abstract":"<p><p>Cell-free RNA (cfRNA) is emerging as a supplemental approach for liquid biopsy (LBx). Given that lymphoid cells and plasma cells express substantial quantities of immunoglobulin (Ig) and T-cell receptor (TCR) RNA, we investigated the utility of using cfRNA for detecting B-cell and T-cell clonality in LBxs. Using next-generation sequencing (NGS) of cfRNA, we clonotyped Igs and TCRs in LBx samples from patients with B-cell neoplasm, T-cell neoplasm, myeloid neoplasm and solid tumors alongside cancer-free individuals. To establish a clonality cutoff, we clonotyped tissue RNA from patients with confirmed clonal B- or T-cell and from polyclonal. Clonotype-naïve testing of LBx samples demonstrated B-cell clonality in 36% of B-cell neoplasms, 7% of normal, 8% of T-cell lymphomas, 13% of myeloid neoplasms, and 14% of solid tumors. T-cell clonality using TCR beta or gamma demonstrated T-cell clonality in 22% of T-cell neoplasms, 3% of normal, 5% of myeloid neoplasms, 7% of solid tumors and 3% of B-cell neoplasms. This confirms that Clonotype-naïve cfRNA testing in LBx is a reliable approach for detecting B- and T-cell clonality.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}