Blood最新文献

{"title":"Mevalonate Metabolism Orchestrates Platelet Hyperactivation via Protein Prenylation to Aggravate Septic Thrombosis","authors":"Haojie Jiang,Mina Yang,Tong Yu,Chen Ding,Junwei Fang,Bing Zhao,Wenjuan Bai,Xuying Yin,Zizhong Zeng,Jing Wang,Xuefeng Wang,Jing Dai,Junling Liu,Yanyan Xu","doi":"10.1182/blood.2026034576","DOIUrl":"https://doi.org/10.1182/blood.2026034576","url":null,"abstract":"Sepsis is a life-threatening systemic inflammatory disorder that triggers disseminated intravascular coagulation and microthrombosis, in which exaggerated platelet activation exacerbates disease progression. The mevalonate pathway is responsible for the biosynthesis of vital isoprenoids and sterols, also playing an important role in the prenylation modification of proteins. We found the mevalonate metabolic pathway is highly activated in platelets during infection. The interruption of this pathway, using platelet specific mevalonate kinase deficiency mice model, could significantly suppress platelet activation and NETosis, alleviating sepsis-induced intravascular thrombosis. Mechanistically, we identified prenylated proteins in platelets and found prenylation level of small GTPases, such as Rap1, were increased after sepsis, indicating the important role of protein prenylation in platelet hyperactivation during sepsis. Notably, the binding level of Rap1 and Talin-1 was significantly impaired in MVK deficient platelets, showing that Rap1-Talin-1 interaction is crucial for MVA-mediated platelet activation. Furthermore, as inhibitors of prenyl diphosphate synthase, the lipophilic bisphosphonates TH-Z145 and TH-Z93 exerted potent effects in alleviating platelet activation and septic thrombosis, as well as prolonging survival in sepsis mice. Collectively, targeting the MVA pathway provides a novel therapeutic strategy for sepsis-triggered thrombosis and platelet activation.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"36 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088548","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":"New FDA-Approved Treg Therapy to Reduce Chronic GVHD After Allogeneic HSCT","authors":"Nelson J. Chao","doi":"10.1182/blood.2026035591","DOIUrl":"https://doi.org/10.1182/blood.2026035591","url":null,"abstract":"The Precision-T phase 3 trial is the first randomized, multicenter demonstration that a centrally manufactured defined allograft is effective markedly reducing moderate-to-severe chronic GVHD and non-relapse mortality without loss of graft versus leukemia or graft failure and infection. The engineered graft appears to instruct immune reconstitution toward a regulated, tolerance-associated state, giving the product a mechanism for further studies. The question is how far we can further program it.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"14 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088546","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":"DMT1 Facilitates Heme-iron Absorption in Rats and Mice","authors":"Yue He,Jacob S Shine,Sitara Sriram,Li-Ying Kuo,Melissa Fraga,Laura M Garrick,Michael D Garrick,Iqbal Hamza,James F Collins","doi":"10.1182/blood.2026034352","DOIUrl":"https://doi.org/10.1182/blood.2026034352","url":null,"abstract":"Mechanisms of heme-iron (HI) absorption remain uncertain. Heme is probably absorbed by receptor-mediated endocytosis; iron is then enzymatically liberated from heme within endosomes, or in the cytosol. If heme is catabolized in endosomes, a transporter, such as DMT1, would be required to export ionic iron into the cytosol. Here, we tested the hypothesis that intestinal DMT1 functions in the HI absorption pathway. The first experimental approach utilized Belgrade (b) rats, expressing dysfunctional DMT1 protein, and the second used conditional, intestine-specific DMT1 KO mice. HI absorption experiments were carried out with radiolabeled, donor rat RBCs, containing ~98% of iron as HI and with >94% of activity in 59Fe-heme. Iron-deficient, anemic +/b (control) rats absorbed 10.8% of a peroral dose of 59Fe-heme within 24 hours, while similarly anemic b/b rats absorbed 1.4% (an 8-fold reduction). Notably, serum hepcidin levels were invariable between both groups of rats (and 10x lower than controls). Moreover, ablation of intestinal DMT1 led to iron-restricted erythropoiesis and severe anemia in adolescent mice weaned on to nonheme iron (NHI) or HI diets. DMT1 was also required to upregulate 59Fe-heme absorption in iron-deficient, anemic mice. DMT1 thus facilitates the absorption of both main forms of dietary iron, NHI and HI.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"58 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088547","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":"Measuring factor VIII after gene therapy: which assay?","authors":"Michiel Coppens","doi":"10.1182/blood.2026035382","DOIUrl":"https://doi.org/10.1182/blood.2026035382","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"21 1","pages":"1761-1762"},"PeriodicalIF":20.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092352","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":"Menin inhibitors unleash JUND-mediated resistance mechanisms","authors":"Vassilena Sharlandjieva,Thomas A. Milne","doi":"10.1182/blood.2026035278","DOIUrl":"https://doi.org/10.1182/blood.2026035278","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"5 1","pages":"1759-1760"},"PeriodicalIF":20.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088604","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":"Better together in\u0000 NPM1\u0000 -mutated AML","authors":"Christoph Röllig","doi":"10.1182/blood.2026034978","DOIUrl":"https://doi.org/10.1182/blood.2026034978","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"8 1","pages":"1755-1756"},"PeriodicalIF":20.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088553","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":"Lu J, Xue S, Wang Y, et al. Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML. Blood. 2025;145(22):2645-2655.","authors":"","doi":"10.1182/blood.2026035742","DOIUrl":"https://doi.org/10.1182/blood.2026035742","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 14","pages":"1854"},"PeriodicalIF":23.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104191","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":"Ziftomenib with venetoclax and azacitidine for relapsed/refractory NPM1-mutated acute myeloid leukemia.","authors":"Eunice S Wang, Harry Erba, Amer M Zeidan, Gail J Roboz, Jessica K Altman, Anjali S Advani, Tara L Lin, Stephen A Strickland, Mark B Juckett, Keith W Pratz, James K Mangan, Christine M McMahon, Leonard C Alsfeld, Suresh Kumar Balasubramanian, Guru Subramanian Guru Murthy, Marcello Rotta, Neil D Palmisiano, James McCloskey, Antoine N Saliba, Mohamad Khawandanah, Yazan F Madanat, Kiran Naqvi, Ayman H Qasrawi, Gary J Schiller, Talha Badar, Ivana Gojo, George Yaghmour, Diaa Osman, Hongling Zhang, Ying Tian, Harris S Soifer, Marcie Riches, Daniel Corum, Mollie Leoni, Amir T Fathi, Ghayas C Issa","doi":"10.1182/blood.2026034043","DOIUrl":"10.1182/blood.2026034043","url":null,"abstract":"<p><strong>Abstract: </strong>Ziftomenib, a potent, selective, oral menin inhibitor, is approved as monotherapy for adults with relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML). The KOMET-007 phase 1 trial investigated clinical activity and tolerability of ziftomenib in combination with standard therapies for R/R and newly diagnosed AML. Here, we report the outcomes of adults with R/R NPM1-m AML treated with ziftomenib plus venetoclax/azacitidine. In phase 1a, patients received ziftomenib 200, 400, or 600 mg once daily with standard doses of venetoclax/azacitidine. In phase 1b, ziftomenib 600 mg was selected for expansion. A total of 67 patients were treated (27 phase 1a; 40 phase 1b). Median age was 66 years; 55% were male. Median number of previous therapies was 1 (range, 1-8); 55% received previous venetoclax, and 22% had received previous transplantation. Most common (≥20%) grade ≥3 treatment-emergent adverse events were leukopenia (34%), thrombocytopenia (28%), febrile neutropenia and neutropenia (25% each). Six patients developed corrected QT prolongation (1 ziftomenib-related; grade 1), and 2 experienced differentiation syndrome (grade 3); all events were successfully managed. In patients receiving ziftomenib 600 mg, composite complete remission (CRc) rate was 46% (22/48), with 67% (12/18) achieving central measurable residual disease (MRD) negativity (<0.01% threshold). In venetoclax-naïve and -exposed patients, CRc rates were 70% (16/23) and 24% (6/25), with MRD negativity rates of 75% (9/12) and 50% (3/6), respectively. Median duration of response was 8.6 months, and median overall survival was not reached. The combination of ziftomenib 600 mg with venetoclax/azacitidine was well tolerated with deep and durable clinical activity in R/R NPM1-m AML. This trial was registered at www.clinicaltrials.gov as NCT05735184.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1775-1788"},"PeriodicalIF":23.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142718","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":"Enhanced factor VIII activation accelerates thrombin generation and hemostatic potency in mice","authors":"Lacramioara Ivanciu,Mettine H.A. Bos,Sudharsan Parthasarathy,Raffaella Toso,Rodney M. Camire","doi":"10.1182/blood.2026034984","DOIUrl":"https://doi.org/10.1182/blood.2026034984","url":null,"abstract":"Factor VIII (FVIII) circulates as an inactive procofactor and is converted to its active form (FVIIIa) by proteolytic cleavage at Arg372, Arg740, and Arg1689. Although these cleavage events are well characterized, their individual contributions to FVIII activation and hemostatic function remain incompletely defined. To address this, we engineered a FVIII variant (FVIII-2RKR) in which the B-domain and acidic region 3 region were replaced with a PACE/furin processing site, generating a molecule that requires only cleavage at Arg372 for conversion to FVIIIa. FVIII-2RKR exhibited markedly increased apparent activity in plasma-based assays, shortened thrombin generation lag time, and enhanced factor Xa (FXa) generation compared with B-domain-deleted FVIII, whereas both proteins were functionally equivalent following thrombin activation. FVIII-2RKR was cleaved more rapidly at Arg372 by thrombin and FXa, demonstrating that processing at Arg740 and Arg1689 regulates the rate of Arg372 cleavage rather than directly contributing to cofactor activity. In hemophilia A mice, FVIII-2RKR consistently enhanced early hemostatic function across ferric chloride, laser injury, and tail bleeding models, achieving improved efficacy at lower doses. Despite reduced half-life due to impaired von Willebrand factor (vWF) binding, FVIII-2RKR remained effective in vWF-deficient mice, indicating that vWF is not required for local FVIII function at sites of vascular injury. Together, these findings define distinct roles for FVIII activation cleavage sites and demonstrate that processing at Arg740 and Arg1689 regulates activation through Arg372, linking the rate of FVIII activation to hemostatic efficacy in vivo.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"8 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092353","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":"Wagner DL, Elsallab M, Maus MV. Promises and potential pitfalls of in vivo CAR gene therapy. Blood. 2026;148(5):535-544.","authors":"","doi":"10.1182/blood.2026036165","DOIUrl":"https://doi.org/10.1182/blood.2026036165","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 14","pages":"1854"},"PeriodicalIF":23.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104160","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}