Blood最新文献

{"title":"Immunoactinopathies revisited: understanding clinical manifestations and biological pathways.","authors":"Fleur Hiensch, Loïc Dupré, Elisabeth Salzer","doi":"10.1182/blood.2024026763","DOIUrl":"10.1182/blood.2024026763","url":null,"abstract":"<p><strong>Abstract: </strong>Immune cell functionality is highly dependent on the actin cytoskeleton. The actin cytoskeleton is regulated by a complex molecular machinery that involves multiple genes. Mutations in these genes can cause inborn errors of immunity, also termed immunoactinopathies, of which Wiskott-Aldrich syndrome is the best-characterized entity. Currently, mutations in 23 genes can be considered causative of immunoactinopathies. Immunoactinopathies are rare disease entities with complex combinations of clinical manifestations, including immunodeficiency, immune dysregulation, malignancies, atopy, thrombocytopenia and bleeding, skin involvement, or congenital defects. Prompt diagnosis is crucial, because hematopoietic stem cell transplantation in an early phase can offer cure and prevent further complications. This review provides a detailed summary of the clinical experience with immunoactinopathies so far, elaborates on the most distinguishing features of immunoactinopathies by providing a clinical categorization, and links this information to the underlying biological pathways. This information may be of help to clinicians in the diagnosis of patients and to eventually improve patient care.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2709-2732"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456674","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":"STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL.","authors":"Jason Xu, Jonathan H Sussman, Austin Yang, Satoshi Yoshimura, Jianzhong Hu, Changya Chen, Tiffaney Vincent, Shovik Bandyopadhyay, Elizabeth Y Li, Tristan Lim, Omar Elghawy, Adam Barsouk, Damjan Karanfilovski, Shira L Wald, Gregory M Chen, David Wu, Haley Newman, Alexander Li, Yusha Sun, Chia-Hui Chen, Kathrin Bernt, Brent L Wood, Stuart S Winter, Kimberly P Dunsmore, Elizabeth Raetz, Meenakshi Devidas, Stanley Pounds, Mignon Loh, Stephen P Hunger, Mark Y Chiang, Caroline Diorio, Danika Di Giacomo, Petri Pölönen, Charles G Mullighan, Jun J Yang, Kai Tan, David T Teachey","doi":"10.1182/blood.2025028566","DOIUrl":"10.1182/blood.2025028566","url":null,"abstract":"<p><strong>Abstract: </strong>We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children's Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2793-2798"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656096","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":"Classic Hodgkin lymphoma in the cerebellum: a rare site for a common disease.","authors":"Yukiko Kitagawa, Elaine S Jaffe","doi":"10.1182/blood.2025028992","DOIUrl":"10.1182/blood.2025028992","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 23","pages":"2799"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224217","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":"Reactivation of developmentally silenced globin genes through forced linear recruitment of remote enhancers.","authors":"Anna-Karina Felder, Sjoerd J D Tjalsma, Han J M P Verhagen, Rezin Majied, Marjon J A M Verstegen, Thijs C J Verheul, Jeffrey van Haren, Rebecca Mohnani, Richard Gremmen, Peter H L Krijger, Sjaak Philipsen, Emile van den Akker, Wouter de Laat","doi":"10.1182/blood.2024028128","DOIUrl":"https://doi.org/10.1182/blood.2024028128","url":null,"abstract":"<p><p>The human genome contains regulatory DNA elements, enhancers, that can activate gene transcription over long chromosomal distances. Here, we show that enhancer distance can be critical for gene silencing. We demonstrate that linear recruitment of the normally distal strong HBB enhancer to developmentally silenced embryonic HBE or fetal HBG promoters, through deletion or inversion of intervening DNA sequences, results in their strongly reactivated expression in adult erythroid cells and ex vivo differentiated hematopoietic stem and progenitor cells. A similar observation is made in the HBA locus, where deletion-to-recruit of the distal enhancer strongly reactivates embryonic HBZ expression. Overall, our work assigns function to seemingly non-regulatory genomic segments: by providing linear separation they may support genes to autonomously control their transcriptional response to distal enhancers.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207687","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":"Hitting the Therapeutic Bullseye with Targeted Therapy for Patients with Chronic Lymphocytic Leukemia.","authors":"William G Wierda, Barbara F Eichhorst, Michael J Hallek","doi":"10.1182/blood.2025028570","DOIUrl":"https://doi.org/10.1182/blood.2025028570","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is a disease of great clinical and biologic heterogeneity; some patients are observed for years without symptoms, while others rapidly develop progressive disease requiring treatment. With therapy, some patients eventually develop resistant CLL or transformation to an aggressive form. Across this spectrum, patients experience immune dysfunction associated with increased risk for infection and second cancers, contributing to morbidity and mortality of the disease. The ultimate therapeutic bullseye for CLL is to eliminate the disease and achieve immune restoration. Disease elimination can potentially be achieved for a fraction of patients treated first-line with chemoimmunotherapy (FCR), for some patients who receive time-limited combined targeted therapy, and for some patients with relapsed/refractory CLL who undergo allogeneic stem cell transplant. Long-term immune restoration for these patients is elusive. Current targeted therapies, including BTK- and BCL2-inhibitors and CD20 monoclonal antibodies used in combinations, can produce exceptional therapeutic outcomes, which are improving survival for patients who need treatment. While clear progress has been made toward highly effective CLL management, appreciation of the full impact of these advances will require time due to the chronic nature of the disease. Additionally, it is imperative to ensure global access to the targeted therapies, emphasizing the need for harmonized regulatory oversight and affordable treatment options worldwide. Here, we discuss research and collaborative strategies to refine the use of targeted agents to eliminate CLL and restore immune function for all affected individuals.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207686","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":"Phase 1/2 Trial of Anti-CD7 Allogeneic WU-CART-007 in patients with Relapsed/Refractory T-cell Malignancies.","authors":"Armin Ghobadi, Ibrahim Aldoss, Shannon L Maude, Deepa Bhojwani, Alan S Wayne, Ashish Bajel, Bhagirathbhai Dholaria, Rawan G Faramand, Ryan J Mattison, Anita W Rijneveld, C Michel Zwaan, Friso G Calkoen, André Baruchel, Nicolas Boissel, Michael P Rettig, Brent Wood, Kenneth Jacobs, Stephanie Christ, Haley Irons, Ben Capoccia, Deborah Masters, Justo Gonzalez, Tony Wu, Maria Del Rosario, Alexander Hamil, Ouiam Bakkacha, John Muth, Brett Ramsey, Eileen McNulty, Jan Baughman, Matthew L Cooper, Jan K Davidson-Moncada, John F DiPersio","doi":"10.1182/blood.2025028387","DOIUrl":"https://doi.org/10.1182/blood.2025028387","url":null,"abstract":"<p><p>Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3+3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 28 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Two grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred (3.8%). One grade 2 immune effector cell associated HLH-like syndrome (IEC-HS) was observed. Among the 11 patients evaluable for response at the RP2D who received enhanced lymphodepleting chemotherapy, the overall response rate was 90.9% and composite complete remission rate was 72.7%. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186551","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":"Role of allo-HCT in \"nonclassical\" MPNs and MDS/MPNs: recommendations from the PH&G Committee and the CMWP of the EBMT.","authors":"Nicola Polverelli, Juan Carlos Hernández-Boluda, Francesco Onida, Carmelo Gurnari, Kavita Raj, Tomasz Czerw, Michelle Kenyon, Marie Robin, Katja Sockel, Annalisa Ruggeri, Isabel Sánchez-Ortega, Daniel A Arber, Luca Arcaini, Fernando Barroso Duarte, Giorgia Battipaglia, Yves Chalandon, Fabio Ciceri, Nicholas C P Cross, Joanna Drozd-Sokolowska, Vaneuza Funke, Nico Gagelmann, Naseema Gangat, Jason Gotlib, Paola Guglielmelli, Claire Harrison, Gabriela Hobbs, Tania Jain, Joseph D Khoury, Jean Jacques Kiladjian, Nicolaus Kröger, Luca Malcovati, Massimo Martino, Ruben Mesa, Attilio Orazi, Eric Padron, Francesca Palandri, Francesco Passamonti, Mrinal M Patnaik, Naveen Pemmaraju, Deepti H Radia, Andreas Reiter, Domenico Russo, Christof Scheid, Ayalew Tefferi, Alessandro M Vannucchi, Daniel H Wiseman, Ibrahim Yakoub-Agha, Donal P McLornan","doi":"10.1182/blood.2024028000","DOIUrl":"10.1182/blood.2024028000","url":null,"abstract":"<p><strong>Abstract: </strong>\"Nonclassical\" myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a heterogeneous group of malignancies characterized by a wide range of clinical manifestations. Unlike classical MPNs, there is no standardized management approach for these conditions, particularly concerning the indications for and management of allogeneic hematopoietic cell transplantation. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) have collaborated to develop shared guidelines aimed at optimizing the selection and management of patients with these rare forms of neoplasms. A comprehensive review of the literature from the publication of the revised fourth edition of the (2016) World Health Organization classification onward was conducted. A multidisciplinary group of experts in the field convened to produce this document, which was developed through multiple rounds of draft circulation. Key recommendations include the early identification of potential transplant candidates, particularly in cases of chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL)/CEL, not otherwise specified (CEL-NOS), myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions with FGFR1, JAK2, ABL1, and FLT3 rearrangements, MDS/MPN with neutrophilia/atypical chronic myeloid leukemia, and MDS/MPN, NOS. For patients with MPN, NOS/MPN unclassifiable, standard recommendations for myelofibrosis should be applied. Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended on the basis of established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2561-2573"},"PeriodicalIF":21.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662466","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":"It's high TIM-3 for armored CAR-T therapy for B-ALL.","authors":"Alexandros Rampotas, Claire Roddie","doi":"10.1182/blood.2025028491","DOIUrl":"https://doi.org/10.1182/blood.2025028491","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 22","pages":"2538-2540"},"PeriodicalIF":21.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172657","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":"SPI-ing on human B-cell development.","authors":"Stuart G Tangye","doi":"10.1182/blood.2025028405","DOIUrl":"https://doi.org/10.1182/blood.2025028405","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 22","pages":"2535-2536"},"PeriodicalIF":21.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172673","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":"Unveiling the enigma: circulating flowerlike large B-lymphoma cells in the context of angioimmunoblastic T-cell lymphoma.","authors":"Bhaumik Shah, Reza Nejati","doi":"10.1182/blood.2025028521","DOIUrl":"https://doi.org/10.1182/blood.2025028521","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 22","pages":"2671"},"PeriodicalIF":21.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172678","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}