Blood最新文献_第10页

Not in the beginning. 一开始没有。

IF 23.1 1区医学

Blood Pub Date : 2025-09-11 DOI: 10.1182/blood.2025029865

Andrew Yee

引用次数: 0

Masthead Subscription 报头订阅

IF 20.3 1区医学

Blood Pub Date : 2025-09-11 DOI: 10.1016/s0006-4971(25)01946-9

引用次数: 0

Mac-Man clearance of alloreactive T cells in GVHD. GVHD中同种异体反应性T细胞的Mac-Man清除。

IF 20.3 1区医学

Blood Pub Date : 2025-09-11 DOI: 10.1182/blood.2025029647

Nataliya Prokopenko Buxbaum

引用次数: 0

ClpP: a new Achilles' heel in myeloma. ClpP：骨髓瘤的新致命弱点。

IF 20.3 1区医学

Blood Pub Date : 2025-09-11 DOI: 10.1182/blood.2025029682

Antonio Sacco,Aldo M Roccaro

引用次数: 0

Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation. 肠道hepcidin过表达可促进缺铁性贫血，并通过下调DMT1来抵消铁超载。

IF 20.3 1区医学

Blood Pub Date : 2025-09-09 DOI: 10.1182/blood.2025028370

Marion Falabrègue,Candice Aurrand,Léa Cazaulon,Nadia Boussetta,Sara Zumerle,Zoubida Karim,Nouzha Djebrani-Oussedik,Joel Poupon,Sandra Guilmeau,Emeric Dupe,Anne Aucouturier,Philippe Langella,Luis G Bermudez-Humaran,Sophie Vaulont,Carole Peyssonnaux

{"title":"Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation.","authors":"Marion Falabrègue,Candice Aurrand,Léa Cazaulon,Nadia Boussetta,Sara Zumerle,Zoubida Karim,Nouzha Djebrani-Oussedik,Joel Poupon,Sandra Guilmeau,Emeric Dupe,Anne Aucouturier,Philippe Langella,Luis G Bermudez-Humaran,Sophie Vaulont,Carole Peyssonnaux","doi":"10.1182/blood.2025028370","DOIUrl":"https://doi.org/10.1182/blood.2025028370","url":null,"abstract":"Hepcidin is the key hyposideremic hormone produced primarily by the liver. However, recent reports reveal extra-hepatic functional sources of hepcidin, including the intestine, the site of dietary iron absorption. To determine whether intestinal hepcidin may play a role in plasma iron lowering, we generated transgenic mice overexpressing the peptide specifically in this tissue. At one month of age, transgenic mice exhibited severe iron deficiency along with decreased haematological indices and a drastic suppression of liver hepcidin in response to hyposideremia. Mechanistically, we showed that intestinal hepcidin was produced in the intestine lumen, inducing a striking down-regulation of Divalent Metal Transporter 1 (DMT1) protein at the enterocyte. To confirm the capacity of hepcidin to decrease DMT1, we developed food-grade recombinant lactic acid bacteria (recLAB) genetically modified to deliver hepcidin directly into the intestinal lumen. These recLAB induced a rapid decrease of duodenal DMT1 and, most importantly, when daily orally administrated, protected against iron overload in a mouse model of hemochromatosis. Taken together, our data reveal a previously unrecognized role of intestinal hepcidin as a regulator of systemic iron homeostasis, acting on DMT1 on the apical side of enterocytes, with potential therapeutics relevance for haematological or iron disorders.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"16 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026019","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}

引用次数: 0

Isatuximab for Relapsed and/or Refractory AL Amyloidosis: Results of a Prospective Phase 2 Trial (SWOG S1702). Isatuximab治疗复发和/或难治性AL淀粉样变性：一项前瞻性2期试验（SWOG S1702）的结果

IF 20.3 1区医学

Blood Pub Date : 2025-09-09 DOI: 10.1182/blood.2024027962

Terri Parker,Adam Landon Rosenthal,Vaishali Sanchorawala,Heather J Landau,Erica L Campagnaro,Prashant Kapoor,Natalia Neparidze,Saulius K Girnius,Patrick Hagen,Emma C Scott,Antje Hoering,Brian G M Durie,Robert Z Orlowski

{"title":"Isatuximab for Relapsed and/or Refractory AL Amyloidosis: Results of a Prospective Phase 2 Trial (SWOG S1702).","authors":"Terri Parker,Adam Landon Rosenthal,Vaishali Sanchorawala,Heather J Landau,Erica L Campagnaro,Prashant Kapoor,Natalia Neparidze,Saulius K Girnius,Patrick Hagen,Emma C Scott,Antje Hoering,Brian G M Durie,Robert Z Orlowski","doi":"10.1182/blood.2024027962","DOIUrl":"https://doi.org/10.1182/blood.2024027962","url":null,"abstract":"Isatuximab is an IgG1k monoclonal antibody that binds with high affinity to CD38 expressed on plasma cells. Anti-CD38 antibodies have shown efficacy as monotherapy and in combination in a variety of settings for patients with multiple myeloma and light chain (AL) amyloidosis. This multi-center, cooperative group phase 2 trial was designed to evaluate hematologic response, organ response, and safety of isatuximab monotherapy for the treatment of relapsed AL amyloidosis. Isatuximab at 20 mg/kg was administered intravenously weekly during the first 28-day cycle and then every other week during cycles 2-24. Forty-three patients were registered, with 35 patients being evaluable for response. The overall hematologic response rate was 77.1%, with 57% of patients achieving a VGPR or better. The median time to partial response or better was 1.1 months. Renal response occurred in 50% (7/14) of patients with renal involvement and cardiac response occurred in 57% (8/14) of patients who were evaluable utilizing NT-pro-BNP with cardiac involvement. The most common treatment related grade ≥3 adverse events included lymphopenia (n=3, 8.5%) and infection (n=2, 6%). Isatuximab demonstrated substantial efficacy in previously treated patients with AL amyloidosis and was associated with a good safety profile. This trial was registered at www.clinicaltrials.gov as NCT#03499808.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"49 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025312","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}

引用次数: 0

Fixed-Duration Epcoritamab Plus R2 Drives Favorable Outcomes in Relapsed or Refractory Follicular Lymphoma. 固定时间依可利他单抗+ R2治疗复发或难治性滤泡性淋巴瘤的有利结果

IF 20.3 1区医学

Blood Pub Date : 2025-09-08 DOI: 10.1182/blood.2025029909

Lorenzo Falchi,Anna Sureda,Sirpa Leppä,Joost Sp Vermaat,Marcel Nijland,Jacob Haaber Christensen,Sven de Vos,Harald Holte,Reid W Merryman,Pieternella J Lugtenburg,Pau Abrisqueta,Kim Linton,Gauri Sunkersett,Daniela Hoehn,Ali Rana,Aqeel Abbas,Jennifer Marek,Yi Hao,Andrew J Steele,Christopher Morehouse,Martin Hutchings,David Belada

{"title":"Fixed-Duration Epcoritamab Plus R2 Drives Favorable Outcomes in Relapsed or Refractory Follicular Lymphoma.","authors":"Lorenzo Falchi,Anna Sureda,Sirpa Leppä,Joost Sp Vermaat,Marcel Nijland,Jacob Haaber Christensen,Sven de Vos,Harald Holte,Reid W Merryman,Pieternella J Lugtenburg,Pau Abrisqueta,Kim Linton,Gauri Sunkersett,Daniela Hoehn,Ali Rana,Aqeel Abbas,Jennifer Marek,Yi Hao,Andrew J Steele,Christopher Morehouse,Martin Hutchings,David Belada","doi":"10.1182/blood.2025029909","DOIUrl":"https://doi.org/10.1182/blood.2025029909","url":null,"abstract":"Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody approved as monotherapy for relapsed/refractory (R/R) follicular lymphoma (FL). We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE® NHL-2 (phase 1b/2; NCT04663347). Patients received epcoritamab (2 step-up doses, then 48-mg full doses) for up to 2 years and R2 for up to 12 cycles (28 days/cycle). Primary endpoint was overall response rate (ORR) per investigator assessment (Lugano criteria). As of September 21, 2024, 108 patients received ≥1 epcoritamab dose in expansion (median follow-up, 28.2 months). Median age was 65 years; 57% had 1 prior line of therapy. ORR and complete response (CR) rate were 96% and 88%; CR rates in patients with high-risk features were 90% (primary refractory), 82% (refractory to anti-CD20 and an alkylating agent), and 83% (disease progression within 24 months of first-line therapy). Two-year estimates for remaining in CR, progression-free survival, overall survival, and not starting next antilymphoma therapy were 82%, 76%, 90%, and 84%, respectively. Minimal residual disease negativity was observed in 86% of evaluable patients (clonoSEQ® assay). Common treatment-emergent adverse events (TEAEs) included neutropenia (65%), COVID-19 (59%), and cytokine release syndrome (CRS; 51%). Grade (G) ≥3 TEAEs occurred in 87% of patients; 5 had G5 TEAEs (all COVID-19). CRS events were mostly low grade (38% G1, 11% G2, 2% G3), all resolved, and none led to epcoritamab discontinuation. Fixed-duration epcoritamab plus R2 demonstrated deep, durable responses with manageable safety and favorable outcomes in R/R FL, irrespective of risk features.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"71 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018112","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}

引用次数: 0

Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging. 血小板因子4 （PF4）调控造血干细胞衰老

IF 23.1 1区医学

Blood Pub Date : 2025-09-08 DOI: 10.1182/blood.2024027432

Sen Zhang, Charles E Ayemoba, Anna M Di Staulo, Kenneth Joves, Chandani M Patel, Eva Hin Wa Leung, Maura Lima Pereira Bueno, Xiaoping Du, Mortimer Poncz, Sang-Ging Ong, Claus Nerlov, Maria Maryanovich, Constantinos Chronis, Sandra Pinho

{"title":"Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging.","authors":"Sen Zhang, Charles E Ayemoba, Anna M Di Staulo, Kenneth Joves, Chandani M Patel, Eva Hin Wa Leung, Maura Lima Pereira Bueno, Xiaoping Du, Mortimer Poncz, Sang-Ging Ong, Claus Nerlov, Maria Maryanovich, Constantinos Chronis, Sandra Pinho","doi":"10.1182/blood.2024027432","DOIUrl":"10.1182/blood.2024027432","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) responsible for blood cell production and their bone marrow regulatory niches undergo age-related changes, impacting immune responses and predisposing individuals to hematologic malignancies. Here, we show that the age-related alterations of the megakaryocytic niche and associated downregulation of Platelet Factor 4 (PF4) are pivotal mechanisms driving HSC aging. PF4-deficient mice display several phenotypes reminiscent of accelerated HSC aging, including lymphopenia, increased myeloid output, and DNA damage, mimicking physiologically aged HSCs. Remarkably, recombinant PF4 administration restored old HSCs to youthful functional phenotypes characterized by improved cell polarity, reduced DNA damage, enhanced in vivo reconstitution capacity, and balanced lineage output. Mechanistically, we identified LDLR and CXCR3 as the HSC receptors transmitting the PF4 signal, with double knockout mice showing exacerbated HSC aging phenotypes similar to PF4-deficient mice. Furthermore, human HSCs across various age groups also respond to the youthful PF4 signaling, highlighting its potential for rejuvenating aged hematopoietic systems. These findings pave the way for targeted therapies aimed at reversing age-related HSC decline with potential implications in the prevention or improvement of the course of age-related hematopoietic diseases.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022898","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}

引用次数: 0

CUX1 restrains latent hematopoietic stem cell plasticity by suppressing stem cell-intrinsic inflammatory pathways. CUX1通过抑制干细胞内在炎症通路抑制造血干细胞的潜在可塑性。

IF 20.3 1区医学

Blood Pub Date : 2025-09-08 DOI: 10.1182/blood.2024026815

Tanner C Martinez,Matthew R M Jotte,Saira Khan,Angela Stoddart,Hunter Z Blaylock,Ankit Malik,Megan E McNerney

{"title":"CUX1 restrains latent hematopoietic stem cell plasticity by suppressing stem cell-intrinsic inflammatory pathways.","authors":"Tanner C Martinez,Matthew R M Jotte,Saira Khan,Angela Stoddart,Hunter Z Blaylock,Ankit Malik,Megan E McNerney","doi":"10.1182/blood.2024026815","DOIUrl":"https://doi.org/10.1182/blood.2024026815","url":null,"abstract":"Long-term maintenance of somatic stem cells relies on precise regulation of self-renewal and differentiation. Understanding the molecular framework for these homeostatic processes is essential for improved cellular therapies and treatment of myeloid neoplasms. CUX1 is a widely expressed, dosage-sensitive transcription factor crucial in development and frequently deleted in myeloid neoplasia in the context of -7/(del7q). Here, using novel mouse models and single-cell approaches, we report that dynamic and distinct CUX1 levels are integral to hematopoietic stem cell (HSC) activity. Knockdown of CUX1 reverses HSC differentiation and strikingly re-endows progenitors with stem cell function, accompanied by restoration of the HSC transcriptome and DNA accessibility landscape. CUX1 mediates these activities, in part, via suppressing endogenous retroelements (EREs) and the ensuing interferon-stimulated gene expression program. Both EREs and the interferon response are upregulated in CUX1-deficient acute myeloid leukemia (AML), suggesting a conserved role of CUX1 in regulating these elements. These data establish an unexpected entwinement of stem cell-intrinsic innate immune activation and the transcriptional programs of stem cell identity. Further, we reveal the profound effects of transcription factor levels in cell fate.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"24 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018114","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}

引用次数: 0

Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy. 核呼吸因子1在蛋白酶体抑制治疗下促进多发性骨髓瘤细胞存活。

IF 20.3 1区医学

Blood Pub Date : 2025-09-08 DOI: 10.1182/blood.2025028441

Tiziana Bruno,Maria Chiara Cappelletto,Clelia Cortile,Stefano Di Giovenale,Bruno Amadio,Francesca De Nicola,Italia Falcone,Stefano Giuliani,Belinda Palermo,Valeria Catena,Ludovica Ciuffreda,Fulvia Cerruti,Paolo Cascio,Roberta Merola,Serena Masi,Valentina De Pascale,Ombretta Annibali,Silvia Ferraro,Svitlana Gumenyuk,Francesco Pisani,Francesco Marchesi,Andrea Mengarelli,Maurizio Fanciulli,Giacomo Corleone

{"title":"Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy.","authors":"Tiziana Bruno,Maria Chiara Cappelletto,Clelia Cortile,Stefano Di Giovenale,Bruno Amadio,Francesca De Nicola,Italia Falcone,Stefano Giuliani,Belinda Palermo,Valeria Catena,Ludovica Ciuffreda,Fulvia Cerruti,Paolo Cascio,Roberta Merola,Serena Masi,Valentina De Pascale,Ombretta Annibali,Silvia Ferraro,Svitlana Gumenyuk,Francesco Pisani,Francesco Marchesi,Andrea Mengarelli,Maurizio Fanciulli,Giacomo Corleone","doi":"10.1182/blood.2025028441","DOIUrl":"https://doi.org/10.1182/blood.2025028441","url":null,"abstract":"Multiple myeloma (MM) continues to be an incurable malignancy, even with recent therapeutic advancements. While epigenetic dysregulation at cis-regulatory elements is known to drive disease progression, the complete molecular mechanisms underlying these alterations are poorly understood. Using ATAC-seq analysis combined with computational footprinting of CD138+ cells from 55 MM patients, we depicted the dynamic changes in chromatin accessibility during disease progression and identified Nuclear Respiratory Factor 1 (NRF1) as a master regulator of vital MM survival pathways. We demonstrated that NRF1 maintains proteasome homeostasis by orchestrating the ubiquitination pathway, which is essential for MM cell survival. We discovered a novel enhancer element that physically interacts with the NRF1 promoter, sustaining its expression. Targeting this enhancer RNA reduced NRF1 levels and increased tumor cell sensitivity to bortezomib (BTZ), suggesting therapeutic potential. In xenograft models, we showed that antisense oligonucleotides (ASOs) targeting the NRF1 enhancer, either alone or combined with BTZ, significantly decreased tumor burden and improved survival. Our findings reveal a previously unknown NRF1-dependent mechanism regulating MM cell survival and present a promising therapeutic approach through manipulation of its regulatory network.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"34 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018113","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}

引用次数: 0