Blood最新文献

{"title":"B-lymphoblastic leukemia with KMT2A rearrangement with mature B-cell phenotype and surface λ light-chain restriction.","authors":"Pratik Q Deb,Xinmin Zhang","doi":"10.1182/blood.2025029108","DOIUrl":"https://doi.org/10.1182/blood.2025029108","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"242 1","pages":"3194"},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488100","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":"Aberrant single-cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma.","authors":"Matteo Claudio Da Vià, Francesca Lazzaroni, Antonio Matera, Alessio Marella, Akihiro Maeda, Claudio De Magistris, Loredana Pettine, Antonio Giovanni Solimando, Vanessa Desantis, Giuseppe M Peretti, Laura Mangiavini, Riccardo Giorgino, Sonia Fabris, Stefania Pioggia, Alfredo Marchetti, Marzia Barbieri, Silvia Lonati, Alessandra Cattaneo, Marta Tornese, Margherita Scopetti, Emanuele Calvi, Nayyer Latifinavid, Giancarlo Castellano, Federica Torricelli, Antonino Neri, Cathelijne Fokkema, Tom Cupedo, Marta Lionetti, Francesco Passamonti, Niccolò Bolli","doi":"10.1182/blood.2024025643","DOIUrl":"10.1182/blood.2024025643","url":null,"abstract":"<p><strong>Abstract: </strong>Multiple myeloma (MM) is driven by clonal plasma cell (cPC)-intrinsic factors and changes in the tumor microenvironment (TME). To investigate whether residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNA sequencing (scRNA-seq) and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 21 healthy donors (HDs). Of 234 789 PCs, 64 432 were genotypically identified as pPCs with frequencies decreasing over different disease stages, from 23.66% in monoclonal gammopathy of undetermined significance to 3.23% in MMs (P = .00012). Both cPCs and pPCs had a comparable expression of typical lineage markers (ie, CD38 and CD138), whereas others were more variable (CD27 and ITGB7). Only cPCs overexpressed oncogenes (eg, CCND1/2 and NSD2), but CCND3 was often expressed in pPCs. B-cell maturation antigen was expressed on both pPCs and cPCs, whereas GPRC5D was mostly upregulated in cPCs with implications for on-target, off-tumor activity of targeted immunotherapies. In comparison with HDs, pPCs from patients showed upregulated autophagy and disrupted interaction with TME. Importantly, interferon-related pathways were significantly enriched in pPCs from patients vs HDs (adjusted P < .05) showing an inflamed phenotype affecting genotypically normal PCs. The function of pPCs was consequently affected and correlated with immunoparesis, driven by disrupted cellular interactions with TME. Leveraging our scRNA-seq data, we derived a \"healthy PC signature\" that could be applied to bulk transcriptomics from the CoMMpass data set and predicted significantly better progression-free survival and overall survival (log-rank P < .05 for both). Our findings show that genotypic sc identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"3124-3138"},"PeriodicalIF":21.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514588","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":"Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis.","authors":"Juan Carlos Hernández-Boluda, Adrián Mosquera-Orgueira, Luuk Gras, Linda Koster, Joe Tuffnell, Nicolaus Kröger, Massimiliano Gambella, Thomas Schroeder, Marie Robin, Katja Sockel, Jakob Passweg, Igor Wolfgang Blau, Ibrahim Yakoub-Agha, Ruben Van Dijck, Mattias Stelljes, Henrik Sengeloev, Jan Vydra, Uwe Platzbecker, Moniek de Witte, Frédéric Baron, Kristina Carlson, Javier Rojas, Carlos Pérez Míguez, Davide Crucitti, Kavita Raj, Joanna Drozd-Sokolowska, Giorgia Battipaglia, Nicola Polverelli, Tomasz Czerw, Donal P McLornan","doi":"10.1182/blood.2024027287","DOIUrl":"10.1182/blood.2024027287","url":null,"abstract":"<p><strong>Abstract: </strong>With the incorporation of effective therapies for myelofibrosis (MF), accurately predicting outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for determining the optimal timing for this procedure. Using data from 5183 patients with MF who underwent first allo-HCT between 2005 and 2020 at European Society for Blood and Marrow Transplantation centers, we examined different machine learning (ML) models to predict overall survival after transplant. The cohort was divided into a training set (75%) and a test set (25%) for model validation. A random survival forests (RSF) model was developed based on 10 variables: patient age, comorbidity index, performance status, blood blasts, hemoglobin, leukocytes, platelets, donor type, conditioning intensity, and graft-versus-host disease prophylaxis. Its performance was compared with a 4-level Cox regression-based score and other ML-based models derived from the same data set, and with the Center for International Blood and Marrow Transplant Research score. The RSF outperformed all comparators, achieving better concordance indices across both primary and postessential thrombocythemia/polycythemia vera MF subgroups. The robustness and generalizability of the RSF model was confirmed by Akaike information criterion and time-dependent receiver operating characteristic area under the curve metrics in both sets. Although all models were prognostic for nonrelapse mortality, the RSF provided better curve separation, effectively identifying a high-risk group comprising 25% of patients. In conclusion, ML enhances risk stratification in patients with MF undergoing allo-HCT, paving the way for personalized medicine. A web application (https://gemfin.click/ebmt) based on the RSF model offers a practical tool to identify patients at high risk for poor transplantation outcomes, supporting informed treatment decisions and advancing individualized care.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"3139-3152"},"PeriodicalIF":21.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717944","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":"Association of Epstein-Barr virus genomic alterations with human pathologies.","authors":"Htet Thiri Khine,Yoshitaka Sato,Motoharu Hamada,Miki Umeda,Akira Iizuka,Shika Son,Haruto Arai,Yuki Kojima,Takahiro Watanabe,Azumi Naruse,Kimitoshi Goto,Koichi Ohshima,Yuta Akutsu,Masato Nakaguro,Akira Satou,Hiromi Kataoka,Yoshinori Ito,Akihisa Sawada,Seiichi Kato,Jun-Ichi Kawada,Takayuki Murata,Yusuke Okuno,Hiroshi Kimura","doi":"10.1182/blood.2024028055","DOIUrl":"https://doi.org/10.1182/blood.2024028055","url":null,"abstract":"Epstein-Barr virus (EBV) infects over 90% of humans and is associated with both hematological and epithelial malignancies. Here, we analyzed 990 EBV genomes (319 newly sequenced and 671 from public databases) from patients with various diseases to comprehensively characterize genomic variations, including single nucleotide variations (SNVs) and structural variations (SVs). While most SNVs were a result of conservative evolution and reflected the geographical origins of the viral genomes, we identified several convergent SNV hotspots within the central homology domain of EBNA3B, the transactivation domain of EBNA2, and the second transmembrane domain of LMP1. These convergent SNVs appear to fine-tune viral protein functionality and immunogenicity. SVs, particularly large deletions, were frequently observed in chronic active EBV disease (28%), EBV-positive diffuse large B-cell lymphoma (48%), extranodal NK/T-cell lymphoma (41%), and Burkitt lymphoma (25%), but were less common in infectious mononucleosis (11%), post-transplant lymphoproliferative disorder (7%), and epithelial malignancies (5%). In hematological malignancies, deletions often targeted viral microRNA clusters, potentially promoting viral reactivation and lymphomagenesis. Non-deletion SVs, such as inversions, were also prevalent, with several inversions disrupting the C promoter to suppress latent gene expression, thereby maintaining viral dormancy. Furthermore, recurrent EBNA3B deletions suggested that this viral transcription factor functions as a tumor suppressor. EBNA3B knockout experiments in vitro revealed downregulation of human tumor suppressors, including PTEN and RB1, which could explain the enhanced lymphomagenesis observed in EBNA3B-deficient lymphoblastoid cell line xenografts. Our findings highlight both disease-specific and general contributions of EBV genomic alterations to human cancers, particularly in hematological malignancies.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"635 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488108","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":"Hallmarks of T-cell exhaustion and antigen experience are absent in multiple myeloma from diagnosis to maintenance therapy.","authors":"Carolyn Shasha, David R Glass, Ernest Moelhman, Laura Islas, Yuan Tian, Tony Chour, Guoyue Xu, Gregory L Szeto, Tao Peng, Xiaoling Song, Michelle Wurscher, Andrew J Cowan, Thomas F Bumol, Troy R Torgerson, Philip D Greenberg, Damian J Green, Evan W Newell","doi":"10.1182/blood.2024025655","DOIUrl":"10.1182/blood.2024025655","url":null,"abstract":"<p><strong>Abstract: </strong>Dysregulation of the bone marrow (BM) niche in multiple myeloma (MM) alters the composition and state of resident immune cells, potentially impeding antitumor immunity. One common mechanism of immune inhibition in solid tumors is the induction of exhaustion in tumor-specific T cells. However, the extent of T-cell exhaustion is not well characterized in MM. As the specific mechanisms of immune evasion are critical for devising effective therapeutic strategies, we deeply profiled the CD8+ T-cell compartment of patients with newly diagnosed MM (NDMM) for evidence of T-cell activation and exhaustion. We applied single-cell multiomic sequencing and mass cytometry to longitudinal BM and peripheral blood (PB) samples taken from time points spanning from diagnosis to induction therapy, autologous stem cell transplant, and maintenance therapy. We identified an exhausted-like population that lacked several canonical exhaustion markers, was not significantly enriched in patients with NDMM, and consisted of small, nonpersistent clonotypes. We also observed an activated population with increased frequency in the PB of patients with NDMM exhibiting phenotypic and clonal features consistent with homeostatic, cytokine-driven activation. As an orthogonal measurement of T-cell exhaustion, we performed intracellular cytokine staining and found that patients with NDMM lacked functionally exhausted T cells. In summary, there was no evidence of \"tumor-experienced\" T cells displaying hallmarks of terminal exhaustion and/or antigen-driven activation/expansion in patients with NDMM at any time point.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"3113-3123"},"PeriodicalIF":21.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751119","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":"It takes 2 to inflame: microbiota and genotype shape CGD IBD.","authors":"Rui A Carvalho,M Margarida Souto-Carneiro","doi":"10.1182/blood.2025029443","DOIUrl":"https://doi.org/10.1182/blood.2025029443","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"17 1","pages":"3069-3072"},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488102","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":"A controlled trial for preventing priapism in sickle cell anemia: hydroxyurea plus placebo vs hydroxyurea plus tadalafil.","authors":"Ibrahim M Idris, Aminu A Yusuf, Ismail I Ismail, Awwal M Borodo, Mustapha S Hikima, Shehu A Kana, Tukur Aliyu, Kabiru Musangedu, Atiku Umar Jibrilla, Sani A Aji, Aisha Kuliya-Gwarzo, Kabir Mohammad, Jamil A Galadanci, Rukayya Alkassim, Mohammad A Suwaid, Nafiu Hussaini, Mark Rodeghier, Arthur L Burnett, Michael R DeBaun","doi":"10.1182/blood.2024027898","DOIUrl":"10.1182/blood.2024027898","url":null,"abstract":"<p><strong>Abstract: </strong>Recurrent ischemic priapism is a common complication of sickle cell anemia (SCA) and is associated with devastating physical and psychosocial consequences. All previous trials for priapism prevention have failed to demonstrate clear efficacy. We conducted a randomized, controlled, double-blind phase 2 feasibility trial comparing fixed moderate-dose hydroxyurea plus placebo (usual-care arm) with fixed moderate-dose hydroxyurea plus tadalafil (experimental arm) in 64 males (aged 18-40 years) with at least 3 episodes of SCA-related priapism in the past 12 months. Priapism data were obtained via daily text messages to the participants. The trial's primary outcome measures were 100% recruitment, 98.4% retention, and 93.5% adherence rates. Over a median of 10 months (interquartile range, 3-12), 2.5 and 3.02 priapism events per participant-month were recorded in the usual-care and the experimental arms, with an incidence rate ratio of 0.8 (95% confidence interval [CI], 0.3-1.9; P = .654). The rates of serious adverse events (P = .999) and hospitalization (P = .289) were similar in the 2 arms. Sperm concentration, motility, and normal morphology significantly decreased on hydroxyurea therapy but recovered to prehydroxyurea levels 3 months after therapy cessation. Post hoc, single-arm, pre-post analysis showed a 58.3% priapism incidence rate reduction in the usual-care arm (5.9-2.5 events per month; difference, 3.4; 95% CI, 1.1-5.8; P = .005) and a 66.3% priapism reduction in the experimental arm (8.9-3.02 events per month; difference, 5.9; 95% CI, 3.4-8.5; P < .001) compared with the prerandomization rates. A randomized controlled trial for priapism prevention is feasible in men with SCA. This trial was registered at www.clinicaltrials.gov as #NCT05142254.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"3101-3112"},"PeriodicalIF":21.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613285","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":"NO (nitric oxide) to priapism with hydroxyurea and tadalafil.","authors":"Kenneth I Ataga","doi":"10.1182/blood.2025028905","DOIUrl":"https://doi.org/10.1182/blood.2025028905","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"242 1","pages":"3063-3064"},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488103","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":"An AI model of transplantation risk for myelofibrosis.","authors":"Simón Méndez-Ferrer","doi":"10.1182/blood.2025028816","DOIUrl":"https://doi.org/10.1182/blood.2025028816","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"8 1","pages":"3068-3069"},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488107","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":"When the silence speaks: T-cell dysfunction in myeloma.","authors":"Mirco J Friedrich,Marc S Raab","doi":"10.1182/blood.2025029262","DOIUrl":"https://doi.org/10.1182/blood.2025029262","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"21 1","pages":"3064-3066"},"PeriodicalIF":20.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488152","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}