Blood最新文献

{"title":"The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort.","authors":"Quentin Neven,Chloé Arfeuille,Aurélie Caye-Eude,Pauline Durand,Elodie Lainey,Odile Fenneteau,Brigitte Nelken,Marie Nolla,Arthur Sterin,Audrey Grain,Céline Khouri,Mathieu Simonin,Marie-Emilie Dourthe,Mony Fahd,Fréderic Millot,Bénédicte Neven,Arnaud Petit,Sylvie Chevret,Jean-Hugues Dalle,André Baruchel,Hélène Cavé,Marion Strullu","doi":"10.1182/blood.2025029916","DOIUrl":"https://doi.org/10.1182/blood.2025029916","url":null,"abstract":"Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive pediatric myeloproliferative neoplasm for which hematopoietic stem cell transplantation (HSCT) is currently the only established curative therapy. However, a watch-and-wait (W&W) approach has shown promise for long-term survival in selected cases. In this real-world study, we analyzed outcomes of JMML patients initially managed with a W&W strategy within a nationwide cohort of 161 genetically characterized cases. W&W was chosen for 35 patients, with increasing adoption over time, reaching 39% in the 2016-2021 period. Most patients carried mutations in CBL (43%), NRAS (34%), or homozygous germline SH2B3 (14%). Over a median follow-up of 6.5 years, 86% (30/35) achieved long-term survival with partial or complete resolution of myeloproliferative symptoms, although clonal hematopoiesis persisted in nearly all survivors (28/30). Disease progression occurred in five patients (CBL: n=3, NRAS: n=1, PTPN11: n=1), mostly within two years post-diagnosis. Overall, in the W&W cohort, the 5-year OS and EFS were 93.1% and 84.5%. In NRAS-mutated cases, age <30 months, normal to slightly elevated fetal hemoglobin, platelet >45x109/L, the absence of additional somatic mutations and low DNA methylation profile were associated with favorable outcomes. In CBL-driven JMML, no predictive factor of adverse evolution was identified. Notably, W&W was effective in all patients with homozygous germline SH2B3, regardless of clinical or biological presentation. These findings support W&W as a viable alternative in up to 30% of JMML patients, potentially sparing them from HSCT-associated risks. Given the persistence of clonal hematopoiesis and the risk of extra-hematological complications, long-term monitoring remains essential.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"38 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089778","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":"Immunochemotherapy for older patients with ATLL: a new option?","authors":"Ambroise Marçais","doi":"10.1182/blood.2025029797","DOIUrl":"https://doi.org/10.1182/blood.2025029797","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"80 1","pages":"1379-1380"},"PeriodicalIF":20.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078131","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":"BAP1/TP53 loss defines a BCL-xL-dependent erythroleukemia.","authors":"Tzu-Chieh Ho,Reuben Kapur","doi":"10.1182/blood.2025030074","DOIUrl":"https://doi.org/10.1182/blood.2025030074","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"77 1","pages":"1385-1387"},"PeriodicalIF":20.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078126","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":"Factor XIII: driving (cross-)links in hemostasis, thrombosis, and disease.","authors":"James P Luyendyk, Matthew J Flick, Alisa S Wolberg","doi":"10.1182/blood.2024025321","DOIUrl":"10.1182/blood.2024025321","url":null,"abstract":"<p><strong>Abstract: </strong>Blood clots are complex structures composed of blood cells and proteins held together by a structural framework provided by an insoluble fibrin network. Factor (F)XIII is a protransglutaminase essential for stabilizing the fibrin network. Activated FXIII(a) introduces novel covalent cross-links within and between fibrin and other plasma and cellular proteins and thereby promotes fibrin biochemical and mechanical integrity. These irreversible modifications are also major determinants of clot composition and functional properties. As such, FXIII has central roles in hemostasis and wound healing, thrombosis, and many proinflammatory diseases associated with coagulation activation. The biochemical properties of FXIII are as interesting as its biology is unusual, giving rise to unique and still undefined mechanisms. Here, we review features underlying FXIII biology, biochemical function, biophysical impact, and (patho)physiologic implications in hemostasis, thrombosis, and disease.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1412-1421"},"PeriodicalIF":23.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051774","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 phase 2 trial of CHOP with anti-CCR4 antibody mogamulizumab for older patients with adult T-cell leukemia/lymphoma.","authors":"Makoto Yoshimitsu, Ilseung Choi, Shigeru Kusumoto, Mototsugu Shimokawa, Atae Utsunomiya, Youko Suehiro, Tomonori Hidaka, Kisato Nosaka, Hidenori Sasaki, Shinya Rai, Shinobu Tamura, Satsuki Owatari, Ki-Ryang Koh, Daisuke Nakamura, Masahito Tokunaga, Masaaki Sekine, Yuma Sakamoto, Hiroshi Inagaki, Takashi Ishida, Kenji Ishitsuka","doi":"10.1182/blood.2024027902","DOIUrl":"10.1182/blood.2024027902","url":null,"abstract":"<p><strong>Abstract: </strong>No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14) for older patients with untreated ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56 to 65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary end point was 1-year progression-free survival (PFS). Secondary end points were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CC chemokine receptor 4 (CCR4) mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician's discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval, 24.9-47.6), with a median follow-up of 1.6 years. The 1-year OS and EFS were 66.0% and 29.9%, respectively. CR and ORR were 64.6% and 91.7%. No unexpected toxicities were observed. Of 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAEs were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, although the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for this patient population. This trial was registered at https://jrct.mhlw.go.jp/en-top as #jRCTs041180130.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1440-1449"},"PeriodicalIF":23.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075845","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":"Platelet activation and signaling in thrombus formation.","authors":"Frauke Swieringa, Johan W M Heemskerk, Alice Assinger","doi":"10.1182/blood.2024025320","DOIUrl":"10.1182/blood.2024025320","url":null,"abstract":"<p><strong>Abstract: </strong>In thrombosis and hemostasis, the formation of a platelet-fibrin thrombus or clot is a highly controlled process that varies, depending on the pathological context. Major signaling pathways in platelets are well established. However, studies with genetically modified mice have identified the contribution of hundreds of additional platelet-expressed proteins in arterial thrombus formation and bleeding. Using phenotype information of 540 mouse genes, involved in arterial thrombosis and hemostasis, we review current insights into established and novel platelet signaling mechanisms. We discuss pathways involved in platelet adhesion, shape change, integrin activation, intracellular vesicle trafficking and protein processing, granule secretion, aggregate formation, and procoagulant activity. Specific attention is paid to the signaling routes used by immunoreceptor tyrosine-based activation motif linked, immunoreceptor tyrosine-based inhibitory motif linked, and G protein-coupled receptors, as well as downstream events feeding into GTPase regulation and protein kinase activation. We further summarize known alterations in platelet responses under conditions of venous, inflammatory, and infection-dependent thrombosis, taking into account interactions of platelets with the endothelium, leukocytes, and red blood cells. Understanding the genes and proteins involved in platelet signaling in the context of hemostasis, thrombosis, and inflammation may lead to improved therapies to prevent and treat thrombotic disorders.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1400-1411"},"PeriodicalIF":23.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051028","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":"Structure-based design of therapeutics to control hemostasis.","authors":"Luke J Tucker, Krista Hilmas, Ashley C Brown","doi":"10.1182/blood.2024025323","DOIUrl":"10.1182/blood.2024025323","url":null,"abstract":"<p><strong>Abstract: </strong>Hemorrhage causes millions of deaths and hundreds of billions of dollars in medical costs every year, and a large percentage of trauma bleeding-associated deaths occur in the prehospital setting. Bleeding is typically treated with transfused blood products, but this is difficult in the prehospital setting due to limitations in transportation and storage, especially in rural and remote military settings. Advancements in cold-stored platelets and lyophilized blood products have the potential to address some of these limitations. However, devising novel products that continue to improve shelf life, portability, scalability, cost, and safety for patients experiencing bleeding in prehospital settings could greatly improve treatment options and patient outcomes. This review primarily focuses on rational design of material-based approaches to develop novel hemostatic agents that strive to meet limitations of current blood products, especially for use in the prehospital setting. Key topics of consideration include how material design can lead to identification of effective therapies that stop bleeding as well as strategies to iterate on existing designs to enhance healing after cessation of bleeding. Improving performance and functionality of existing and emerging materials could be achieved through the incorporation of transglutaminases, growth factors, cellular components, or inorganic molecules. Finally, consideration of patient-specific factors that influence bleeding, such as patient sex and age, through evaluation of therapies in specific populations and/or design of materials targeted for specific patient populations, is a key area for development of next-generation hemostatic materials.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1431-1439"},"PeriodicalIF":23.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708479","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":"Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants.","authors":"Nicholas S Gleadall, Lianne Koets, Olga Shamardina, Jeremy Gollub, Aaron J Gottschalk, Orod Razeghi, Gorka Ochoa-Garay, Jonathan Stephens, Ram Varma, Jennifer Martin, Elias Allara, Colin J Brown, James Daly, Emanuele Di Angelantonio, Shane Grimsley, W Martin Howell, Kati Hyvärinen, Ute Jentsch, Nathalie Kingston, Celina Montemayor, Celeste Moya-Valera, John Ord, Jukka Partanen, David Roberts, Kathleen E Stirrups, Sunitha Vege, Lindsay Walker, Andrea Harmer, Shantanu Kaushikkar, Willem H Ouwehand, C Ellen van der Schoot, Connie M Westhoff, Barbera Veldhuisen, William J Lane","doi":"10.1182/blood.2025028902","DOIUrl":"10.1182/blood.2025028902","url":null,"abstract":"<p><strong>Abstract: </strong>Blood transfusions save millions of lives worldwide each year, yet formation of antibodies against nonself antigens remains a significant problem, particularly in patients who receive frequent transfusions. We designed and tested the Universal Blood Donor Typing (UBDT_PC1) array for automated high-throughput simultaneous typing of human erythrocyte antigens (HEAs), platelet antigens (HPAs), leukocyte antigens (HLAs), and neutrophil antigens to support selection of blood products matched beyond ABO/Rh. Typing samples from 6946 study participants of European, African, Admixed American, South Asian, and East Asian ancestry at 2 different laboratories showed a genotype reproducibility of ≥99% for 17 244 variants, translating to 99.98%, 99.90%, and 99.93% concordance across 338 372 HEA, 53 270 HPA, and 107 094 HLA genotypes, respectively. Compared with previous clinical typing data, concordance was 99.9% and 99.6% for 245 874 HEA and 3726 HPA comparisons, respectively. HLA types were 99.1% concordant with clinical typing across 8130 comparisons, with imputation accuracy higher in Europeans vs non-Europeans. Seven variant RHD alleles, a GYPB deletion underlying the U- phenotype, and 14 high-frequency antigen-negative types were also detected. Beyond blood typing, hereditary hemochromatosis-associated HFE variants were identified in 276 participants. We found that the UBDT_PC1 array can reliably type a wide range of blood cell antigens across diverse ancestries. Reproducibility and accuracy were retained when transfusion-relevant targets from the UBDT_PC1 array were incorporated into the UKBB_v2.2 genome-wide typing array. The results represent the potential for significant advancement toward improved patient care by reducing harm in transfusion recipients through extended matching.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1511-1524"},"PeriodicalIF":23.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274213","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":"Azacitidine as therapy for VEXAS syndrome.","authors":"David P Steensma,Mrinal M Patnaik","doi":"10.1182/blood.2025029732","DOIUrl":"https://doi.org/10.1182/blood.2025029732","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"2674 1","pages":"1380-1382"},"PeriodicalIF":20.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078127","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":"UPS delivers apolarity and senescence to HSCs.","authors":"Hartmut Geiger","doi":"10.1182/blood.2025030420","DOIUrl":"https://doi.org/10.1182/blood.2025030420","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"221 4 1","pages":"1382-1383"},"PeriodicalIF":20.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078132","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}