Blood最新文献

{"title":"Enriched Adaptive Immunity and Reduced Inflammatory Response in Plasma Cell Disorders of Self-Identified Black Patients","authors":"Hongwei Tang,William C Pilcher,Huihuang Yan,Annamalai Sivasankar,Jinzhuang Dou,Suganti Shivaram,Mariam Khanfar,Neeraj Sharma,Stacey J. Lehman,Shulan Tian,Surendra Dasari,Cinthya J Zepeda-Mendoza,Mahek Bai,Joselle Cook,Nadine Abdallah,Abiola Bolarinwa,Emilie I Anderson,Taxiarchis V. Kourelis,S Vincent Rajkumar,Shaji K. Kumar,Megan Weivoda,Felicia Gomez,Manoj Bhasin,Linda B Baughn","doi":"10.1182/blood.2026033998","DOIUrl":"https://doi.org/10.1182/blood.2026033998","url":null,"abstract":"The immune tumor microenvironment (iTME) plays a crucial role in disease biology of plasma cell (PC) dyscrasias, but remains poorly characterized in self-identified Black individuals, a population at increased risk. Mass cytometry and scRNA-seq of 128 bone marrow aspirates revealed significant changes in immune cell composition across the disease spectrum, including shifts from naïve to effector T cells with declines in B cells, MAIT, pDCs, and increases in monocytes with disease progression. Self-identified Black patients had higher relative proportions of terminally differentiated T cells and lower monocytes in newly diagnosed and treated multiple myeloma (MM). ScRNA-seq revealed genes overexpressed in self-identified Black individuals were enriched for E2F targets and G2-M checkpoints, while reduced genes were enriched for TNF-α/NF-kB, interferon and inflammatory responses pathways. These findings were supported by genetic ancestry and validated in an independent dataset of 286 patients with MM from the MMRF Immune Atlas. Self-identified race and African genetic similarity are significantly associated with remodeling the MM iTME, with potential implications for disease biology and treatment response.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"67 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088544","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":"African Genetic Similarity Is Associated with Reduced Inflammation and Enhanced Adaptive Immunity in Multiple Myeloma","authors":"William C Pilcher,Hongwei Tang,Katherine Ferguson,Steven M Foltz,Marina E Michaud,Sarthak Satpathy,Nishi Nilesh Shah,Yuxin Jin,Denis Ohlstrom,Mojtaba Bakhtiari,Chaitanya R Acharya,Immune Atlas Consortium,Alexander M Gout,Jonathan Keats,Madhav V. Dhodapkar,David E. Avigan,Ravi Vij,Shaji K. Kumar,Hearn Jay Cho,Ioannis S Vlachos,Li Ding,Sacha Gnjatic,Craig Emmitt Cole,Ajay K. Nooka,Sagar Lonial,John Carpten,George Mulligan,Linda B Baughn,Manoj Bhasin","doi":"10.1182/blood.2026033999","DOIUrl":"https://doi.org/10.1182/blood.2026033999","url":null,"abstract":"The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"1 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088545","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":"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}