Leukemia最新文献

{"title":"Distinct stromal cell populations define the B-cell acute lymphoblastic leukemia microenvironment","authors":"Mauricio N. Ferrao Blanco, Bexultan Kazybay, Mirjam Belderbos, Olaf Heidenreich, Hermann Josef Vormoor","doi":"10.1038/s41375-025-02734-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02734-z","url":null,"abstract":"<p>The bone marrow microenvironment plays a critical role in B-cell acute lymphoblastic leukemia (B-ALL) progression, yet its cellular heterogeneity remains poorly understood. Using single-cell RNA sequencing on patient-derived bone marrow aspirates from pediatric B-ALL patients, we identified two distinct mesenchymal stromal cell (MSC) populations: early mesenchymal progenitors and adipogenic progenitors. Spatial transcriptomic analysis further revealed the localization of these cell types and identified a third stromal population, osteogenic-lineage cells, exclusively present in the bone biopsy. Functional ex vivo assays using sorted stromal populations derived from B-ALL patient bone marrow aspirates demonstrated that both early mesenchymal and adipogenic progenitors secrete key niche-supportive factors, including CXCL12 and Osteopontin, and support leukemic cell survival and chemoresistance. Transcriptomic profiling revealed that B-ALL cells interact differently with stromal subtypes. Notably, adipogenic progenitors, but not early mesenchymal progenitors, provide support to leukemic cells through interleukin-7 and VCAM1 signaling. Stromal cells from B-ALL patients exhibited an enhanced adipogenic differentiation capacity compared to healthy controls. Moreover, co-culture experiments showed that B-ALL cells induce adipogenic differentiation in healthy MSCs through a cell contact-dependent mechanism. Adipogenic progenitors were also enriched in relapse samples, implicating them in disease progression. These findings highlight the complexity of the B-ALL microenvironment and identify different specialized stromal niches with which the leukemic cells can engage.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"8 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of adult patients with newly diagnosed IDH-mutated AML treated with intensive chemotherapy and venetoclax","authors":"Jennifer Croden,&nbsp;Wei-Ying Jen,&nbsp;Jennifer Marvin-Peek,&nbsp;Lianchun Xiao,&nbsp;Ian M. Bouligny,&nbsp;Sanam Loghavi,&nbsp;Gautam Borthakur,&nbsp;Naval G. Daver,&nbsp;Hussein A. Abbas,&nbsp;Koichi Takahashi,&nbsp;Koji Sasaki,&nbsp;Naveen Pemmaraju,&nbsp;Nicholas J. Short,&nbsp;Danielle Hammond,&nbsp;Elias Jabbour,&nbsp;Lucia Masarova,&nbsp;Kelly S. Chien,&nbsp;Ghayas C. Issa,&nbsp;Guillermo Montalban-Bravo,&nbsp;Musa Yilmaz,&nbsp;Abhishek Maiti,&nbsp;Yesid Alvarado-Valero,&nbsp;Guillermo Garcia-Manero,&nbsp;Farhad Ravandi,&nbsp;Marina Y. Konopleva,&nbsp;Hagop M. Kantarjian,&nbsp;Tapan M. Kadia,&nbsp;Courtney D. DiNardo","doi":"10.1038/s41375-025-02733-0","DOIUrl":"10.1038/s41375-025-02733-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2538-2541"},"PeriodicalIF":13.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms","authors":"Hiroki Kobayashi, Yuta Komizo, Nanami Watanabe, Yu Miyata, Yoshiya Ohnuma, Yasushige Kamimura-Aoyagi, Kanako Yuki, Yoshihiro Hayashi, Minoru Yoshida, Yuka Harada, Hironori Harada","doi":"10.1038/s41375-025-02729-w","DOIUrl":"https://doi.org/10.1038/s41375-025-02729-w","url":null,"abstract":"<p>Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. Megakaryocyte maturation might be an innovative therapeutic strategy because its dysregulation profoundly contributes to MDS pathogenesis. Here, we identified crizotinib, a clinically approved anti-cancer drug for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer, as a potent inducer of megakaryocyte maturation. We demonstrated that crizotinib effectively induced polyploidization to increase the platelet-producing capacity of megakaryocytes derived from an MDS murine model and MDS patients by targeting Aurora kinases rather than its canonical targets, ALK/ROS1/c-MET. Importantly, crizotinib administration substantially ameliorated thrombocytopenia in our preclinical model. Our findings underscore the remarkable potential of crizotinib for drug repurposing and offer a novel therapeutic strategy for MDS patients with thrombocytopenia facing health-related quality of life concerns.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underlying biology, challenges and emergent concepts in the treatment of relapsed and refractory pediatric T-cell acute lymphoblastic leukemia","authors":"Patrícia Amaral, Rhona Christie, Daisy O. F. Gresham, Emma J. M. Lucas, Luyao Kevin Xu, Lena Behrmann, Jonathan Bond, Sofie Degerman, Frederik W. van Delft, Steven Goossens, Melanie Hagleitner, Chris Halsey, Nicholas Jones, Tim Lammens, Frank N. van Leeuwen, Marc R. Mansour, Panagiotis Ntziachristos, David O’Connor, João T. Barata","doi":"10.1038/s41375-025-02723-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02723-2","url":null,"abstract":"<p>Relapsed and refractory disease in children with T-cell acute lymphoblastic leukemia (R/R T-ALL) remains a major clinical challenge. Outcomes for children who relapse or exhibit resistance to initial treatments are dismal, with survival rates frequently below 25% despite aggressive therapy. To minimize toxicities and improve outcomes, individualized precision medicine approaches targeting the underlying biology of R/R T-ALL are especially important, considering that T-ALL is characterized by genetic, epigenetic and posttranscriptional heterogeneity, and organ and niche specificities (e.g. the central nervous system), all of which underlie disease progression and therapy resistance. Here, we summarize the current understanding of the complexity of pediatric T-ALL biology and how such knowledge may be clinically leveraged, emphasizing the need for innovative therapeutic routes to improve outcomes for children with R/R T-ALL. Emerging approaches that hold promise or show palpable results include proteasome inhibitors, BCL-2 antagonists, and JAK (for JAK- and IL-7R-driven cases), ABL and SRC family tyrosine kinase (for LCK-activated cases), MEK or PI3K-mTOR inhibitors. MYC-targeting agents, DNA demethylating agents, histone deacetylase inhibitors, splicing modulators, or drugs exploring T-ALL metabolic vulnerabilities, are other examples for potential pharmacological intervention. Immunotherapies, particularly CAR T-cell products targeting CD7 and other markers, but also biologics (e.g. targeting CD38), are under development and increasing interest. These agents should be rationally integrated into precision medicine combination therapies informed by genetic, epigenetic, and posttranscriptional insights that will be essential to refine risk stratification and minimize the risk of resistance. Novel strategies leveraging artificial intelligence and machine learning could accelerate discovery and optimize treatment frameworks.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"66 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complosome - a key regulator of hematopoietic stem cells and innate immune responses","authors":"Henning Ulrich","doi":"10.1038/s41375-025-02728-x","DOIUrl":"10.1038/s41375-025-02728-x","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2297-2298"},"PeriodicalIF":13.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically associated genomic landscape of pediatric non-Down Syndrome acute megakaryoblastic leukemia in Chinese patients","authors":"Kefei Wu,&nbsp;Hui Liu,&nbsp;Wenting Hu,&nbsp;Yuhan Liu,&nbsp;Wenyan Wu,&nbsp;Bowen Cui,&nbsp;Han Wang,&nbsp;Shuang Zhao,&nbsp;Yanjing Tang,&nbsp;Jiaoyang Cai,&nbsp;Yong Wang,&nbsp;Xiang Wang,&nbsp;Xiaoxiao Chen,&nbsp;Yixiao Mo,&nbsp;Ting Liu,&nbsp;Yangyang Xie,&nbsp;Huiying Sun,&nbsp;Ying Zhong,&nbsp;Jianan Rao,&nbsp;Rongrong Fan,&nbsp;Ying Wang,&nbsp;Changcheng Chen,&nbsp;Zhuo Wang,&nbsp;Ronghua Wang,&nbsp;Yuanlu Huang,&nbsp;Qiaoqiao Shi,&nbsp;Lan Wang,&nbsp;Jing Chen,&nbsp;Jing Chen,&nbsp;Benshang Li,&nbsp;Xiaolong Chen,&nbsp;Yu Liu,&nbsp;Shuhong Shen","doi":"10.1038/s41375-025-02741-0","DOIUrl":"10.1038/s41375-025-02741-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2533-2537"},"PeriodicalIF":13.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards methylation-based redefinition of TAL1 positive T-cell acute lymphoblastic leukaemia (T-ALL)","authors":"Charlotte Smith,&nbsp;Guillaume Charbonnier,&nbsp;Mathieu Simonin,&nbsp;Estelle Balducci,&nbsp;Thomas Steimle,&nbsp;Guillaume P. Andrieu,&nbsp;Agata Cieslak,&nbsp;Marianne Courgeon,&nbsp;Marc LeLorc’h,&nbsp;Anand Mayakonda,&nbsp;Christoph Plass,&nbsp;Aurélie Le Nezet,&nbsp;Mehdi Latiri,&nbsp;Norbert Ifrah,&nbsp;Hervé Dombret,&nbsp;Françoise Huguet,&nbsp;André Baruchel,&nbsp;Elizabeth Macintyre,&nbsp;Arnaud Petit,&nbsp;Nicolas Boissel,&nbsp;Vahid Asnafi,&nbsp;Aurore Touzart","doi":"10.1038/s41375-025-02714-3","DOIUrl":"10.1038/s41375-025-02714-3","url":null,"abstract":"TAL1 is one of the most frequently dysregulated oncogenes in T-cell Acute Lymphoblastic Leukaemia (T-ALL). However, the precise frequency and prognostic impact associated with its dysregulation remains unclear and is confounded by TAL1’s diverse dysregulation mechanisms. TAL1 dysregulation is detected by TAL1 transcript quantification, though this technique may be subject to interference by TAL1 transcripts deriving from residual haematological cells that physiologically express high levels of the gene. We hypothesised TAL1 DNA methylation could provide a more reliable biomarker than TAL1 transcript quantification alone. We extensively studied TAL1 dysregulation in a large adult and paediatric T-ALL cohort (n = 401) and designed a TAL1 specific MS-MLPA assay to determine methylation levels. Whereas monoallelic TAL1 + T-ALL had homogeneous gene expression profiles, never expressed other driver oncogenes and were TAL1 hypomethylated (methylation ratio &lt;0.4), biallelic TAL1 + T-ALL were enriched in expression of other driver oncogenes (TLX1, TLX3, HOXA), and had heterogeneous transcriptomes and TAL1 methylation levels. In PDX analysis, monoallelic TAL1 expression was stable, contrary to biallelic expression which mostly derived from residual non-malignant haematopoietic cells. Importantly, we report 5 novel TAL1 dysregulation mechanisms using long-read nanopore and OGM analysis, and show that TAL1 hypomethylation identifies TAL1 dysregulation, and is associated with worse prognosis.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2344-2354"},"PeriodicalIF":13.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN","authors":"Karl Kapahnke,&nbsp;Thomas Plenge,&nbsp;Tabea Klaus,&nbsp;Manoj K. Gupta,&nbsp;Disha Anand,&nbsp;Tamer T. Önder,&nbsp;Birgit Perner,&nbsp;Tina M. Schnöder,&nbsp;Felicitas R. Thol,&nbsp;Frederik Damm,&nbsp;Florian H. Heidel,&nbsp;Florian Perner","doi":"10.1038/s41375-025-02719-y","DOIUrl":"10.1038/s41375-025-02719-y","url":null,"abstract":"Persistence of JAK2-mutated clones that may undergo clonal evolution and malignant transformation remains a challenge in myeloproliferative neoplasms (MPN), Novel therapeutic approaches to attenuate clonal evolution and progression to blast-phase are therefore urgently needed. LSD1 (KDM1A) inhibitors reduce symptoms and clonal burden in MPN, but whether these compounds may be effective in advanced disease stages remained so far elusive. Using a chromatin-focused CRISPR-Cas9 screen, we identified the histone methyltransferase DOT1L as a synthetic lethal target under pharmacologic LSD1 inhibition. DOT1L knockout impaired cellular fitness, reduced proliferation, and prolonged survival in xenografts. Furthermore, genetic inactivation of DOT1L increased LSD1 inhibitor sensitivity up to 100-fold resulting in cell cycle arrest and apoptosis induction in TP53 mutant blast-phase MPN. Mechanistically, we have identified a novel, non-canonical function of DOT1L which co-occupied LSD1-bound enhancers and contributed to the repression of transcriptional programs independent of its enzymatic activity. DOT1L loss cooperated with LSD1 inhibitors to activate tumor suppressive programs, while pharmacologic inhibition of DOT1Ls catalytic activity failed to elicit comparable effects. These findings indicate that leveraging DOT1L targeting via protein degradation or RNA interference, rather than conventional enzymatic inhibition, could enhance the therapeutic efficacy of LSD1 inhibitors in blast-phase MPN.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2406-2418"},"PeriodicalIF":13.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02719-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous whole-body multi-parametric 2-[18F]FDG-PET/MRI in smoldering multiple myeloma assessment: diagnostic and prognostic impact","authors":"Bastien Jamet,&nbsp;Cyrille Touzeau,&nbsp;Hatem Necib,&nbsp;Éric Frampas,&nbsp;Huajun Sun,&nbsp;Chloe Francois,&nbsp;Nicolas Blin,&nbsp;Thomas Carlier,&nbsp;Aurélien Monnet,&nbsp;Nicoletta Lilli,&nbsp;Caroline Bodet-Milin,&nbsp;Philippe Moreau,&nbsp;Françoise Kraeber-Bodere","doi":"10.1038/s41375-025-02717-0","DOIUrl":"10.1038/s41375-025-02717-0","url":null,"abstract":"The co-primary aims of this study were to assess the diagnostic and prognostic performance of Whole-body-2-[18F]-fluorodeoxyglucose-positron emission tomography coupled with MRI (WB-2-[18F]FDG-PET/MRI) imaging in the smoldering multiple myeloma (SMM) workup for detection of MM-related medullary or extra-medullary disease and for the prediction of progression-free survival (PFS) defined as time to progression to symptomatic MM requiring therapy. A total of 116 patients with SMM (without CRAB or SLiM criteria before imaging) were prospectively included in the study and underwent full multi-parametric WB-2-[18F]FDG-PET/MRI imaging. PET detected at least one FL &gt; 5 mm in 9% of patients compared to 20% on MRI (p = 0.02). PET detected diffuse bone marrow involvement (BMI) in 20% of patients and MRI in 53% (p &lt; 10−3). A total of 98 patients with true SMM not requiring treatment were then followed up. The presence of diffuse BMI on MRI was the strongest adverse prognostic parameter for PFS (univariate: hazard ratio (HR), 6.12; p &lt; 10−2. Multivariate : HR, 4.16; p = 0.03) and could be proposed as a new high-risk biomarker for progression to symptomatic MM. Dynamic contrast-enhanced (DCE)-MRI based increased peak enhancement intensity (PEI) and maximum intensity time ratio (MITR) values were other strong adverse prognostic factors.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2516-2522"},"PeriodicalIF":13.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young unrelated donors confer a survival advantage for patients with myeloid malignancies compared to older siblings","authors":"Johannes Schetelig,&nbsp;Henning Baldauf,&nbsp;Carina Rave,&nbsp;Gesine Bug,&nbsp;Lutz P. Müller,&nbsp;Eva Maria Wagner-Drouet,&nbsp;Francis Ayuketang Ayuk,&nbsp;Wolfgang Bethge,&nbsp;Matthias Stelljes,&nbsp;Thomas Schroeder,&nbsp;Friedrich Stölzel,&nbsp;Edgar Jost,&nbsp;Christoph Schmid,&nbsp;Desiree Kunadt,&nbsp;Katja Sockel,&nbsp;Katharina Egger-Heidrich,&nbsp;Jan Moritz Middeke,&nbsp;Daniel Fürst,&nbsp;Daniel Schefzyk,&nbsp;Jürgen Sauter,&nbsp;Alexander H. Schmidt,&nbsp;Katharina Fleischhauer,&nbsp;Martin Bornhäuser,&nbsp;on behalf of the German Cooperative Transplant Study Group,&nbsp;Deutsches Register für hämatopoetische Stammzelltransplantation und Zelltherapie (DRST)","doi":"10.1038/s41375-025-02724-1","DOIUrl":"10.1038/s41375-025-02724-1","url":null,"abstract":"Donor age is one factor to optimize allogeneic hematopoietic cell transplantation (alloHCT). Therefore, we investigated whether young unrelated donors (UD) provide a benefit for older patients with myeloid malignancies compared to HLA-identical sibling donors (MSD). We performed a retrospective registry study on patients ≥50 years who received a first alloHCT between 2010 and 2020. We compared event-free survival (EFS) of patients who were transplanted from MSD aged ≥50 years versus UD aged ≤35 years who were HLA-compatible for HLA-A, -B, -C, and -DRB1. In total, we analyzed data from 3460 patients. With multivariable adjustment EFS (HR 0.86, p = 0.003), OS (HR 0.82, p &lt; 0.001), and risk of relapse (HR 0.84, p = 0.018) were significantly better for HLA-compatible UD compared to MSD. No survival advantage was found, when UD with unfavorable sex or CMV constellation were compared to MSD with favorable constellations. In a meta-analysis on 9905 patients with myeloid malignancies, including ours, we found reduced risk of relapse (pooled HR 0.78, p = 0.006) and better EFS (pooled HR 0.89, p &lt; 0.001) for young matched UD versus MSD. To select young HLA-compatible UD over older MSD may reduce relapse risk and improve survival for older patients with myeloid malignancies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2523-2532"},"PeriodicalIF":13.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02724-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}