Blood最新文献

{"title":"A tale of two transferrin receptors.","authors":"Xia Xiao, Jodie L Babitt","doi":"10.1182/blood.2026033394","DOIUrl":"https://doi.org/10.1182/blood.2026033394","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 19","pages":"2166-2168"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833488","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 stem and progenitor cell-derived gene expression signature is prognostic for survival in myelofibrosis.","authors":"Jessie J F Medeiros, Andy G X Zeng, Suraj Bansal, Hyerin Kim, Michelle Chan-Seng-Yue, Tristan Woo, Jessica L McLeod, Sagar Kothari, Andrea Arruda, Hubert Tsui, Jaime O Claudio, Dawn Maze, Hassan Sibai, Mark D Minden, James A Kennedy, Christopher Famulare, Raajit K Rampal, Jean C Y Wang, John E Dick, Vikas Gupta","doi":"10.1182/blood.2025030094","DOIUrl":"10.1182/blood.2025030094","url":null,"abstract":"<p><strong>Abstract: </strong>In this study, we hypothesized that transcriptomic features among disease-driving hematopoietic stem and progenitor cells (HSPC) could improve current paradigms for risk stratification in myelofibrosis (MF). Therefore, we performed bulk RNA sequencing (RNA-seq) of blood from 358 patients with MF, split into training and test cohorts. Single-cell RNA-seq data from Lin-CD34+ MF HSPCs were used to guide the development of a prognostic model trained on the bulk RNA-seq data. A NanoString assay was used to validate our final model in 2 independent cohorts of patients with MF. We identified a 24-gene weighted-sum expression score (MPN24) that was prognostic of overall survival (OS). In 2 independent cohorts of 170 and 100 patients with MF, MPN24-high scoring patients had worse 5-year OS compared with MPN24-low scoring patients (25.5% vs 86.9%, hazard ratio [HR] = 9.81, P = 4.0e-11 and 23.5% vs 75.9%, HR, 6.40, P = 1.8e-7, respectively). MPN24-high was also associated with clinical, mutation and karyotypic features known to confer adverse risk in MF. The MPN24 score retained independent prognostic significance in multivariable analysis incorporating these covariates and existing risk stratification models including Dynamic International Prognostic Scoring System (DIPSS), DIPSS plus, Mutation-Enhanced International Prognostic Score System (MIPSS70), and MIPSS70 plus version 2.0, adding significant prognostic value to these risk stratification models (P = 1.6e-5, 4.0e-6, 1.5e-6, and 5.4e-4, respectively). The MPN24 score was particularly useful in improving risk-stratification of DIPSS-intermediate, and MIPSS70-intermediate and high-risk patients. MPN24 is an HSPC-derived gene expression score that is associated with OS independent of clinical and genomic prognostic variables and improves risk stratification in MF.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2238-2251"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892103","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":"Making the case for ruxolitinib in CAR T-cell enterocolitis.","authors":"Mark P Hamilton, Partow Kebriaei","doi":"10.1182/blood.2025032940","DOIUrl":"https://doi.org/10.1182/blood.2025032940","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 19","pages":"2162-2163"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833460","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":"Adding transcriptomic features to MF prognostic models.","authors":"Francesco Passamonti","doi":"10.1182/blood.2025032671","DOIUrl":"https://doi.org/10.1182/blood.2025032671","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 19","pages":"2165-2166"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833478","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":"MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay.","authors":"Jan-Michel Heger, Julia Mattlener, Helen Kaul, Justin Ferdinandus, Jessica Schneider, Julia K Schleifenbaum, Gundolf Schneider, Valdete Schaub, Mathias Hänel, Johannes C Hellmuth, Judith Dierlamm, Sonja Martin, Stephan Mathas, Julia Meissner, D Michiel Pegtel, Josée M Zijlstra, Anna Ossowski, Kerstin Becker, Michael Hallek, Bastian von Tresckow, Peter Borchmann, Sven Borchmann","doi":"10.1182/blood.2025031089","DOIUrl":"10.1182/blood.2025031089","url":null,"abstract":"<p><strong>Abstract: </strong>Beyond cure, major goals in patients with Hodgkin lymphoma (HL) are tailoring treatment to a patient's individual risk for relapse to reduce acute and late toxicities, identifying candidates for early incorporation of novel agents, and making treatment affordable on a global level. Minimal residual disease (MRD) assessment by circulating tumor DNA (ctDNA) sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling time points, assay validation, and definitions for MRD negativity. Here, we applied LymphoVista, a validated ctDNA sequencing assay for genotyping and MRD monitoring in lymphoma, to samples obtained from the German Hodgkin Study Group (GHSG) HD21 trial after 2 cycles of treatment (MRD-2) using a case-cohort design. Patients with positive MRD-2 result were at higher risk for relapse, progression, or death compared with MRD-2-negative patients (4-year progression-free survival [PFS], 36.7% vs 82.2%; hazard ratio, 5.3; 95% confidence interval, 2.0-13.8; P = .0008). After inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 results had 4-year PFS rates of 72.2% vs 95.3%. Combining MRD-2 with positron emission tomography after 2 cycles of BrECADD/eBEACOPP (PET-2) can identify patients at very low and patients at very high risk of relapse, progression, or death. In summary, these results suggest that MRD-2 assessment by LymphoVista allows for early outcome prognostication in patients with HL and could be used as a tool to improve treatment guidance on its own or in conjunction with PET-2.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2194-2202"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149005","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":"NXTAGE: a phase 1/2 study of NXT007 to assess safety, pharmacokinetics, and efficacy in hemophilia A without inhibitors.","authors":"Keiji Nogami, Chur-Woo You, Young-Shil Park, Yeu-Chin Chen, Ming-Ching Shen, Jiaan-Der Wang, Masahiro Takeyama, Kagehiro Amano, Sheng-Chieh Chou, Takuya Miwa, Chun-An Chen, Takeshi Miyake, Keisuke Iwasaki, Ryota Kobayashi, Midori Shima","doi":"10.1182/blood.2025031894","DOIUrl":"10.1182/blood.2025031894","url":null,"abstract":"<p><strong>Abstract: </strong>NXT007 is a next-generation, activated factor VIII (FVIIIa)-mimetic bispecific antibody under investigation in the phase 1/2 NXTAGE trial. Here, we report the primary analysis of the multiple-ascending-dose Part B study in people with hemophilia A (PwHA). Eligible participants were men with severe HA without FVIII inhibitors. Four dose cohorts (B1-B4) were planned, with NXT007 administered subcutaneously at maintenance doses of 0.072 mg/kg, 0.28 mg/kg, 0.70 mg/kg, and 1.08 mg/kg, respectively, every 4 weeks. Primary end points were safety (adverse events [AEs] and serious AEs [SAEs]), tolerability, pharmacokinetics, pharmacodynamics, and efficacy; secondary end points included incidence of anti-drug antibodies (ADAs). Participants in cohorts B1 (n = 10), B2 (n = 6), B3 (n = 6), and B4 (n = 8) had received NXT007 for a median (minimum to maximum) of 114.1 (29-140), 96.4 (88-112), 58.1 (52-72), and 22.2 (4-28) weeks, respectively. Two participants discontinued treatment: NXT007-unrelated AE (n = 1) and complete loss of NXT007 exposure due to ADAs (n = 1). Participants' plasma NXT007 concentration showed a dose-dependent increase, and predicted FVIII-equivalent activity reached a nonhemophilic level (≥40 IU/dL) in B2 onward. NXT007 had a favorable safety profile at all doses. Most AEs were mild/moderate and all 3 SAEs were considered unrelated to NXT007. Mean annualized treated bleed rates were 1.48 (B1), 0.28 (B2), 0.00 (B3), and 0.00 (B4). Two participants had pharmacokinetics-affecting NXT007 ADAs, including the B1 participant who discontinued treatment. NXTAGE Part B demonstrates that NXT007 could provide nonhemophilic coagulation activity in PwHA, with a less burdensome dose regimen than currently available therapies. This trial was registered at Japan Registry of Clinical Trials as jRCT2080224835.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2261-2271"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123806","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":"Generational advancement of factor VIIIa mimetics.","authors":"David Lillicrap","doi":"10.1182/blood.2026033256","DOIUrl":"https://doi.org/10.1182/blood.2026033256","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 19","pages":"2168-2170"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833538","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":"Time of infusion does not significantly impact outcomes following CAR T-cell therapy in large B-cell lymphoma.","authors":"Mark R Dowling, Edward R Scheffer Cliff, Anthony Jeffrey, Catelyn Cashion, Stephen Boyle, Jian Li, Thomas Buss, Ross MacDonald, Anastasia Edelkina, Hamish W Scott, Nicole L O'Leary, Michelle W Keir, Safia Belbachir, David A Westerman, Constantine S Tam, P Joy Ho, Simon J Harrison, Allison Barraclough, Shafqat Inam, Emily Blyth, Andrea S Henden, Vinay Vanguru, Michael J Dickinson","doi":"10.1182/blood.2025032307","DOIUrl":"10.1182/blood.2025032307","url":null,"abstract":"<p><strong>Abstract: </strong>In this retrospective analysis of 584 patients who received chimeric antigen receptor T-cell therapy for large B-cell lymphoma at 6 Australian centers, no association was found between time of infusion and outcome, accounting for confounders, suggesting minimal clinical impact of chronobiology in this setting.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2272-2277"},"PeriodicalIF":23.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212210","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":"Genetics and MRD for therapy allocation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.","authors":"Josep-Maria Ribera, Anna Torrent, Mireia Morgades, Susana Barrena, Jordi Ribera, Eulalia Genesca, José González-Campos, Nuria Martínez-Cibrian, Pau Montesinos, Alberto Hernández Sánchez, Pere Barba, Edgar Zapico, Ricardo Sánchez, Andrés Novo, Marta Sitges, Clara Maluquer Artigal, Esperanza Such, Carmen Botella, Maria Paz Queipo de Llano, Monica Cabrero, Ana Vicent, Paula Lopez de Ugarriza, Mar Tormo, Bernardo-Javier González-González, Irene Garcia-Cadenas, Carlos Rodríguez-Medina, Pilar Martinez Sanchez, Arancha Bermúdez, Ignacio Gómez-Centurión, Maria Herrero-Garcia, Juana Ciudad, Josgrey Navas-Acosta, Lourdes Hermosín, Josefina Serrano, José-Ángel Raposo-Puglia, Laura Solan, Verónica Roldán-Galiacho, Almudena de Laiglesia, Lucía Gómez-Pérez, María Solé-Rodríguez, María-Soledad Casado, Laura Llorente Gonzalez, Daniel Barrios Decoud, Ferrán Vall-Llovera, Jesús-Lorenzo Algarra, Lourdes Amador, Raimundo García-Boyero, Antònia Cladera, Juan Miguel Bergua Burgues, Maria J José Calasanz, Isabel Granada, Evarist Feliu, Jesús-María Hernández-Rivas, Alberto Orfao","doi":"10.1182/blood.2025032645","DOIUrl":"https://doi.org/10.1182/blood.2025032645","url":null,"abstract":"<p><p>In adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) genetic risk is usually combined with measurable residual disease (MRD) assignment to consolidation therapy. However, this combination is not uniform across trials and centralized assessment is not always performed. This study analyzed patients' outcomes using centrally assessed MRD and genetics. Patients with high genetic risk (HGR), those who required two induction cycles for complete remission (CR), and CR patients with end-of-induction (EOI) MRD ≥0.01% were assigned to allogeneic hematopoietic stem cell transplant (alloHSCT), while the remaining patients were assigned to delayed consolidation and maintenance. HGR for B-ALL included KMT2A rearrangements, low hypodiploidy and age >35 years, homozygous TP53 mutations/deletions, or concomitant IKZF1 and CDKN2A/B deletions. HGR in T-ALL included absence of NOTCH1/FBXW7 mutations and/or K/NRAS or PTEN alterations. Patients with early T-ALL (ETP) received a different induction regimen, and all were assigned to alloHSCT. Median (range) age of 436 patients was 39 (18-60) years, 332 with B-lineage ALL and 104 T-ALL. By intention to treat, 243 non-ETP patients (61%) were assigned to alloHSCT and 157 (39%) to CT. The 3-year overall survival (OS) probability (95% CI) was 64% (58%-69%). For patients with CR and EOI MRD<0.01% without HGR (n=109), the OS probability was 81% (70%-89%), compared with 50% (34%-63%) for MRD-negative patients with HGR (n=64). In patients with ETP-ALL the probability of 3-year OS was 61% (37%-79%). The combination of genetics and MRD allows accurate identification of adult Ph- ALL patients candidates to alloHSCT or chemotherapy. The trial was registered at www.ClinicalTrials.gov: NCT04179929.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833457","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":"Inhibiting thromboinflammation via interleukin-4 binding to platelet glycoprotein VI and suppression of thrombosis.","authors":"Shiping Lin, Yuanjie Yin, Shaoying Wang, Chuanfeng Liu, Musan Yan, Xin Jiang, Xin Jin, Qikai Yin, Min Xue, Xiaopeng Tang","doi":"10.1182/blood.2025031889","DOIUrl":"https://doi.org/10.1182/blood.2025031889","url":null,"abstract":"<p><p>Inflammation and coagulation are intricately linked. Although some studies have documented pro-inflammatory drivers of coagulation, the role of anti-inflammatory cytokines and the underlying mechanisms in the modulation of coagulation, platelet function, and thrombosis remain poorly characterized. In this study, we demonstrated that interleukin-4 (IL-4), an anti-inflammatory cytokine, plays a crucial role in regulating platelet function and thrombus formation. IL-4 inhibited collagen-induced intracellular calcium mobilization, P-selectin expression, ATP release, integrin αIIbβ3 activation, platelet spreading, and platelet aggregation. IL-4 binds to residues 38-46 within GPVI's extracellular collagen-binding domain and suppresses downstream signaling by inhibiting phosphorylation of phospholipase Cγ2 and protein kinase C. A GPVI-derived interfering peptide (RR9) binding to IL-4 disrupted the IL-4-GPVI complex and reversed the inhibitory effects of IL-4 on platelets. In vivo, IL-4 overexpression or intravenous administration inhibited platelet intracellular calcium mobilization, ATP release, and aggregation, prolonged bleeding time, and attenuated both arterial and venous thrombosis. Conversely, IL-4 knockout, anti-IL-4 antibody treatment, or RR9 treatment enhanced platelet reactivity, promoted hemostasis, and aggravated thrombosis. Our findings reveal that IL-4 negatively regulates platelet function through direct interaction with GPVI, thereby facilitating crosstalk among inflammation, hemostasis, and thrombosis. Therefore, modulating IL-4 levels provides a novel strategy for treatment of thrombotic disorders.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833490","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}