Blood最新文献

{"title":"Blastic plasmacytoid dendritic cell neoplasm in the absence of cutaneous involvement.","authors":"Naveen Pemmaraju, Sanam Loghavi","doi":"10.1182/blood.2024027086","DOIUrl":"https://doi.org/10.1182/blood.2024027086","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"898"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456700","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":"Deciphering Langerhans cell histiocytosis.","authors":"Julien Haroche, Levi-Dan Azoulay","doi":"10.1182/blood.2024027473","DOIUrl":"https://doi.org/10.1182/blood.2024027473","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"790-791"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456703","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 belt-and-suspenders approach to PNH.","authors":"Gloria F Gerber, Robert A Brodsky","doi":"10.1182/blood.2024027600","DOIUrl":"https://doi.org/10.1182/blood.2024027600","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"785-786"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456694","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 free light chain range decreases LC-MGUS.","authors":"David F Keren","doi":"10.1182/blood.2024027518","DOIUrl":"https://doi.org/10.1182/blood.2024027518","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"788-789"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456705","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":"BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses.","authors":"Giulio Abagnale, Raphaela Schwentner, Philipp Ben Soussia-Weiss, Wouter van Midden, Caterina Sturtzel, Ulrike Pötschger, Magdalena Rados, Sabine Taschner-Mandl, Ingrid Simonitsch-Klupp, Christoph Hafemeister, Florian Halbritter, Martin Distel, Sebastian K Eder, Caroline Hutter","doi":"10.1182/blood.2024026066","DOIUrl":"10.1182/blood.2024026066","url":null,"abstract":"<p><strong>Abstract: </strong>Langerhans cell histiocytosis (LCH) is a clonal hematopoietic disorder defined by tumorous lesions containing CD1a+/CD207+ cells. Two severe complications of LCH are systemic hyperinflammation and progressive neurodegeneration. The scarcity of primary samples and lack of appropriate models limit our mechanistic understanding of LCH pathogenesis and affect patient care. We generated a human in vitro model for LCH using induced pluripotent stem cells (iPSCs) harboring the BRAFV600E mutation, the most common genetic driver of LCH. We show that BRAFV600E/WT iPSCs display myelomonocytic skewing during hematopoiesis and spontaneously differentiate into CD1a+/CD207+ cells that are similar to lesional LCH cells and are derived from a CD14+ progenitor. We show that BRAFV600E modulates the expression of key transcription factors regulating monocytic differentiation and leads to an upregulation of proinflammatory molecules and LCH marker genes early during myeloid differentiation. In vitro drug testing revealed that BRAFV600E-induced transcriptomic changes are reverted upon treatment with mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKis). Importantly, MAPKis do not affect myeloid progenitors but reduce only the mature CD14+ cell population. Furthermore, iPSC-derived neurons (iNeurons) cocultured with BRAFV600E/WT iPSC-derived microglia-like cells, differentiated from iPSC-derived CD34+ progenitors, exhibit signs of neurodegeneration with neuronal damage and release of neurofilament light chain. In summary, the iPSC-based model described here provides a platform to investigate the effects of BRAFV600E in different hematopoietic cell types and provides a tool to compare and identify novel approaches for the treatment of BRAFV600E-driven diseases.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"850-865"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766263","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":"Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graft-versus-host disease.","authors":"Julie R Boiko, Kathleen S Ensbey, Olivia G Waltner, Isaac C Jenkins, Shruti S Bhise, Kelli Pa MacDonald, Bruce R Blazar, Anne Marcie Hall, Ted A Gooley, Simone A Minnie, Stephanie J Lee, Scott N Furlan, Geoffrey R Hill","doi":"10.1182/blood.2024025337","DOIUrl":"https://doi.org/10.1182/blood.2024025337","url":null,"abstract":"<p><p>Chronic graft-versus-host disease (cGVHD) remains the leading cause of non-relapse morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Effective therapeutics agents targeting dysregulated cytokines including IL-17 and CSF-1 have been defined in preclinical models of cGVHD, and efficacy in subsequent clinical trials has led to their recent FDA approval. Despite this, these agents are effective in only a subset of patients, expensive, difficult to access outside the US, and used in a trial-and-error fashion. The ability to readily discern druggable, dysregulated immunity in these patients is desperately needed to facilitate the selection of appropriate treatment and to potentially identify high-risk individuals for preemptive therapy. We used single cell sequencing-based approaches in our informative preclinical cGVHD models to \"reverse engineer\" temporal IL-17 and CSF-1 signatures in mouse blood that could be used to interrogate patients. We defined distinct, non-intuitive IL-17 and CSF-1 signatures in mouse blood monocytes that could be identified in relevant monocytes within 70% of patients at diagnosis of cGVHD and in half of patients at day +100 post-HCT who subsequently developed cGVHD. These signatures can now be evaluated prospectively in clinical studies to help delineate potential responder and non-responders to relevant therapeutics targeting these pathways.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466937","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":"Antibiotics: bad bugs for CAR-T cells?","authors":"Florent Malard, Mohamad Mohty","doi":"10.1182/blood.2024027102","DOIUrl":"https://doi.org/10.1182/blood.2024027102","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"787-788"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456695","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":"Appreciating the oral microbiome's impact on GVHD.","authors":"Maren Schmiester, Robert R Jenq","doi":"10.1182/blood.2024027670","DOIUrl":"https://doi.org/10.1182/blood.2024027670","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"791-793"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456696","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":"Blastoid variant of double-hit lymphoma masquerading as acute lymphoblastic leukemia.","authors":"Muna Al Jabri, Hong Chang","doi":"10.1182/blood.2024027182","DOIUrl":"https://doi.org/10.1182/blood.2024027182","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 8","pages":"897"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456701","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":"Serum free light chains in a racially diverse population including African Americans and populations from South Africa.","authors":"Luca Bertamini, Jean-Baptiste Alberge, David J Lee, Habib El-Khoury, Sungjae Kim, Grace Fleming, Ciara Murphy, Julia Colchie, Maya I Davis, Jacqueline Perry, Elizabeth D Lightbody, Sabine Allam, Lindokuhle N Goqwana, Vinitha Philip, Natalie Smyth, Dhananjay Sakrikar, Mark Perkins, Stephen Harding, Derek Troske, Gad Getz, Elizabeth W Karlson, Nikhil Munshi, Kenneth C Anderson, Lorenzo Trippa, Catherine R Marinac, Wenlong C Chen, Maureen Joffe, Irene M Ghobrial","doi":"10.1182/blood.2024026078","DOIUrl":"10.1182/blood.2024026078","url":null,"abstract":"<p><strong>Abstract: </strong>Detection of light chain (LC) monoclonal gammopathies (MGs) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10 035 individuals for heavy chain MG, identifying 9028 negative cases whose FLC were measured. Participants included 4149 from the PROMISE study (United States, n = 2383; South Africa, n = 1766) and 4879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1074 of 10 035 individuals (10.7%) were diagnosed with LC monoclonal gammopathy of undetermined significance (MGUS), with 99% being κ-restricted. In the United States, 14.8% of Black and 4% of White individuals were diagnosed (P < .01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (P < .01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of AFR descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences. This study includes data from NCT03689595.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"840-849"},"PeriodicalIF":21.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685962","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}