Blood advances最新文献_第8页

Hybridization Capture Long-Read Sequencing & De Novo Assembly of Homologous Haplotypes: A Comprehensive Hemophilia Test. 杂交捕获长读测序和同源单倍型从头组装：一种全面的血友病检测。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-11 DOI: 10.1182/bloodadvances.2025016200

Boyan Liu, Ruixia Xu, Siqian Ma, Mengnan Gu, Lingyin Kong, Lu Zhou, Haoning Liu, Shujin Chen, Yuyan Yang, Ziqiang Yu, Bo Liang, Miao Jiang

{"title":"Hybridization Capture Long-Read Sequencing & De Novo Assembly of Homologous Haplotypes: A Comprehensive Hemophilia Test.","authors":"Boyan Liu, Ruixia Xu, Siqian Ma, Mengnan Gu, Lingyin Kong, Lu Zhou, Haoning Liu, Shujin Chen, Yuyan Yang, Ziqiang Yu, Bo Liang, Miao Jiang","doi":"10.1182/bloodadvances.2025016200","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016200","url":null,"abstract":"Hemophilia is an X-linked bleeding disorder caused by defects in the F8 or F9 genes. Given the wide variety of F8 variants, conventional genetic testing typically requires a combination of multiple methods, and detecting rearrangements in the intron 22 homologous regions (int22h) remains a challenging task. In this study, we developed a comprehensive hemophilia testing program using the PacBio long-read sequencing platform. Experimentally, we established a standard operating procedure for hybridization capture long-read sequencing (hc-LRS), which generates reads longer than 5 kb. Analytically, we employed a suite of bioinformatics tools to identify variants associated with hemophilia, including the detection of int22h-related rearrangements through de novo assembly of homologous haplotypes (DAHH). Our approach successfully identified pathogenic variants in hemophilia patients and carriers, encompassing both single-nucleotide variants (SNVs) and structural variations (SVs), with full concordance to validated methods. Moreover, the program identified complex int22h rearrangements in several samples, which were previously difficult to detect using traditional techniques. Compared to conventional methods, hc-LRS is more cost-effective, convenient, and capable of detecting various variants in a single test. This approach provides a powerful tool for the genetic diagnosis of hemophilia, particularly in patients with unknown genetic backgrounds or complex variants. In conclusion, our comprehensive testing program represents a significant advancement in the genetic diagnosis of hemophilia.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612101","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

Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma. BCMA CAR-T细胞序贯治疗难治性多发性骨髓瘤。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-11 DOI: 10.1182/bloodadvances.2025016712

Tim Richardson, Udo Holtick, Jan Hendrik Frenking, Hishan Tharmaseelan, Hyatt Balke-Want, Ruth Flümann, Elias K Mai, Sandra Sauer, Raphael Teipel, Malte von Bonin, Michael Hallek, Christoph Scheid, Philipp Gödel

{"title":"Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma.","authors":"Tim Richardson, Udo Holtick, Jan Hendrik Frenking, Hishan Tharmaseelan, Hyatt Balke-Want, Ruth Flümann, Elias K Mai, Sandra Sauer, Raphael Teipel, Malte von Bonin, Michael Hallek, Christoph Scheid, Philipp Gödel","doi":"10.1182/bloodadvances.2025016712","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016712","url":null,"abstract":"Multiple myeloma (MM) relapsing after BCMA-directed chimeric antigen receptor T-cell (CAR-T) treatment remains a therapeutic challenge. Data on re-exposure to CAR-T targeting the same antigen are scarce. We analyzed 10 heavily pretreated MM patients at three medical centers treated with the commercially approved CAR-T product ide-cel in a real-world setting. Upon relapse, all patients received cilta-cel as a second CAR-T infusion, with bridging treatments permitted between both therapies. Sequential therapy with BCMA-directed CAR-T therapy was safe, with no higher-grade immune cell-associated side effects or new safety signals. We found robust CAR-T expansion and high response rates (100% ³ VGPR with 60% achieving MRD-negativity) with an estimated progression-free survival 64.8% (95% CI: 39-100%) at 6 months after the second CAR-T treatment. Duration of response to first CAR-T therapy was predictive for durable responses to the second CAR-T product. Loss of BCMA antigen occurred in only one of three patients relapsing after cilta-cel. Two of three relapsing patients died within a year and showed no further response to bispecific antibody treatment. This study provides the first real-world evidence that sequential treatment with two different commercially approved BCMA CAR-T products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR-T therapy.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612106","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

Bing-Neel Syndrome - A Case Series of 46 Patients from the United Kingdom. Bing-Neel综合征——来自英国的46例病例系列。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-11 DOI: 10.1182/bloodadvances.2025016360

Oliver Tomkins, Jahanzaib Khwaja, Shiwen Koay, Nicole Japzon, Chandrashekar Hoskote, Rajeev Gupta, Robert Baker, Jindriska Lindsay, Charalampia Kyriakou, Michael P Lunn, Shirley D'Sa

引用次数: 0

Platelet glycosylation in myelodysplastic syndromes correlates with disease severity. 骨髓增生异常综合征的血小板糖基化与疾病严重程度相关。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-11 DOI: 10.1182/bloodadvances.2025016349

Katelyn E Rosenbalm, Tin Long Wong, Donny Hoang, Valerie L Andersen, George Steinhardt, Shikan Zheng, Elizabeth A Griffiths, Tongjun Gu, Karin M Hoffmeister, Joseph T Lau, Michael J Nemeth

引用次数: 0

Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia. 慢性髓单细胞白血病RAS通路突变的景观和临床病理特征。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-11 DOI: 10.1182/bloodadvances.2025016529

Guillermo Montalban-Bravo, Sanam Loghavi, Ziyi Li, Kelly Sharon Chien, Rashmi Kanagal-Shamanna, Alex Bataller, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Koji Sasaki, Gautam Borthakur, Mahesh Swaminathan, Courtney D DiNardo, Tapan M Kadia, Farhad Ravandi, Naval G Daver, Nicholas J Short, Naveen Pemmaraju, Ghayas C Issa, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford M Csizmar, Hassan B Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, Carlos E Bueso-Ramos, Ayalew Tefferi, Hagop M Kantarjian, Guillermo Garcia-Manero, Mrinal M Patnaik

{"title":"Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia.","authors":"Guillermo Montalban-Bravo, Sanam Loghavi, Ziyi Li, Kelly Sharon Chien, Rashmi Kanagal-Shamanna, Alex Bataller, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Koji Sasaki, Gautam Borthakur, Mahesh Swaminathan, Courtney D DiNardo, Tapan M Kadia, Farhad Ravandi, Naval G Daver, Nicholas J Short, Naveen Pemmaraju, Ghayas C Issa, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford M Csizmar, Hassan B Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, Carlos E Bueso-Ramos, Ayalew Tefferi, Hagop M Kantarjian, Guillermo Garcia-Manero, Mrinal M Patnaik","doi":"10.1182/bloodadvances.2025016529","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016529","url":null,"abstract":"RAS pathway mutations (RASMT) induce proliferative features and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASMT remain unexplored. To characterize the landscape, architecture and implications of unique RASMT in CMML we evaluated a cohort of 814 patients with CMML. We identified 461 RASMT among 342 (42%) patients. N/KRAS and CBL mutations were the most common, frequently involved the P-loop or RING domains, respectively, and frequently appeared as dominant events (63% and 65%, respectively). BRAF, NF1 and PTPN11 mutations spanned throughout the gene structure and frequently appeared as subclonal events (75%, 64%, 59%, respectively). CBL mutations frequently occurred in co-dominance with SRSF2 and multihit TET2 and were enriched for KIT mutations. PTPN11 mutations more frequently co-occurred with SETBP1 and DNMT3A mutations and where infrequently co-dominant with TET2 or ASXL1. RASMT predicted for shorter overall-survival (HR 1.55, 95% CI 1.15-2.07, p=0.0075) and leukemia-free survival (LFS, HR 1.67, 95% CI 1.26-2.20, p=0.0011), influenced outcomes of myelodysplastic and TET2 mutant CMML and cooperated with IDH2 and RUNX1 mutations to induce shorter LFS. This data sets the bases for refined genomic classifications of CMML and underscores the need to develop RAS-directed therapies for patients with CMML.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612103","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

Expression and treatment of ROR1+ cells with bispecific T-cell engagers in pediatric acute lymphoblastic leukemia. ROR1+细胞与双特异性T细胞接合体在儿童急性淋巴细胞白血病中的表达和治疗。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-08 DOI: 10.1182/bloodadvances.2024013814

Paraskevi Diamanti, Bethan K Bailey, Obinna E Iheanacho, John P Moppett, Amit C Nathwani, Allison Blair

{"title":"Expression and treatment of ROR1+ cells with bispecific T-cell engagers in pediatric acute lymphoblastic leukemia.","authors":"Paraskevi Diamanti, Bethan K Bailey, Obinna E Iheanacho, John P Moppett, Amit C Nathwani, Allison Blair","doi":"10.1182/bloodadvances.2024013814","DOIUrl":"10.1182/bloodadvances.2024013814","url":null,"abstract":"Abstract: Receptor tyrosine kinase-like orphan receptor (ROR)1 is overexpressed in some hematological cancers but has low expression in normal tissues, making it a potential therapeutic target. We investigated this therapeutic potential in childhood B-cell precursor (BCP) and T-cell acute lymphoblastic leukemia (T-ALL) cases. The proportion of ROR1+ cells was significantly higher in T-ALL (median, 13.8%; range, 2.9%-87%) than BCP-ALL (6%, 0.3%-83%, P = .02). Antigen density was also lower in BCP-ALL (median, 1027; range, 876-2588) compared to T-ALL (1089, 865-1527). In leukemia propagating cells (LPCs), ROR1 levels were highest in CD34-/CD19+ and CD34-/CD7+ subpopulations. Notably, ROR1+ LPC, in both BCP-ALL and T-ALL, survived induction therapy and their numbers increased post treatment. Subsequently, ROR1 bispecific T-cell engagers (Teng) were tested on primary cases in vitro and in vivo. Addition of ROR1 Teng in vitro reduced ALL survival to 44% in BCP-ALL and 58% in T-ALL, compared to T cells alone (94% and 84%, respectively; P ≤ .01). When NOD.Cg-PrkdcscidIl2rγtm1Wjl/SzJ mice engrafted with primary leukemia were treated with ROR1 Teng, disease burden was reduced by up to 520-fold (from 15.6% to 0.03%) in ROR1+ cells and 68-fold (58% to 0.9%) in CD19+ cells in BCP-ALL. In T-ALL cases, there was a fourfold reduction (from 1.2% to 0.3%) in ROR1+ and 2.3-fold (from 83.7% to 36.7%) in CD7+ levels. This resistance of ROR1+ cells to current therapies makes it an important target. Moreover, as ROR1 Teng were at least comparable to CD19 Teng in vivo, they could be considered for the treatment of refractory BCP-ALL.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3190-3201"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983882","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}

引用次数: 0

Restarting teclistamab and talquetamab after prolonged dose delay may not require re-step-up dosing. 延长剂量延迟后重新启动Teclistamab和Talquetamab可能不需要重新加大剂量。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-08 DOI: 10.1182/bloodadvances.2024015344

Carlyn Rose Tan, Alice Wang, David Nemirovsky, Andriy Derkach, Tala Shekarkhand, Issam Hamadeh, Kylee Maclachlan, Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Alexander Lesokhin, Urvi A Shah, Sridevi Rajeeve, Hamza Hashmi, Dhwani Patel, Ross Firestone, Eric Jurgens, Kevin Miller, Gunjan L Shah, Michael Scordo, Heather J Landau, Sergio A Giralt, Neha Korde, Saad Z Usmani

引用次数: 0

Validation of risk assessment models for venous thromboembolism in patients with cancer receiving systemic therapies. 接受全身治疗的癌症患者静脉血栓栓塞风险评估模型的验证。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-08 DOI: 10.1182/bloodadvances.2025016044

Nikola Vladić, Cornelia Englisch, Julia M Berger, Florian Moik, Anna S Berghoff, Matthias Preusser, Ingrid Pabinger, Cihan Ay

{"title":"Validation of risk assessment models for venous thromboembolism in patients with cancer receiving systemic therapies.","authors":"Nikola Vladić, Cornelia Englisch, Julia M Berger, Florian Moik, Anna S Berghoff, Matthias Preusser, Ingrid Pabinger, Cihan Ay","doi":"10.1182/bloodadvances.2025016044","DOIUrl":"10.1182/bloodadvances.2025016044","url":null,"abstract":"Abstract: Cancer increases the risk of venous thromboembolism (VTE). To identify patients with cancer at high VTE risk who might benefit from primary thromboprophylaxis, several risk assessment models (RAMs) have been developed. The evolution of anticancer treatment, including the implementation of targeted and immunotherapeutic agents, might affect VTE risk and risk prediction. Therefore, we aimed to evaluate the performance of 6 externally validated RAMs (Khorana score, PROTECHT, CONKO, COMPASS-CAT, CATScore, and EHR-CAT) in a prospective observational cohort study of patients with cancer initiating contemporary systemic anticancer therapies. Eight hundred six patients (49.5% female) with a median age of 61 years (interquartile range, 53-69) were included. The most common cancer types were lung (21.8%), breast (10.8%), and pancreatic (10.3%). Anticancer therapies initiated at study inclusion included chemotherapy (48.3%), a combination of chemotherapy and immune checkpoint inhibitor (ICI; 16.6%), ICI monotherapy (15.4%), and targeted agents (19.7%). During an observation period of 6 months, 91 patients experienced a VTE (cumulative incidence, 11.2%; 95% confidence interval [CI], 9.0-13.3). The discriminatory performance of the RAMs varied, with the best c-statistic seen with the CAT Score, whereas the COMPASS-CAT score showed the lowest area under the curve value (c-statistics: Khorana score, 0.53 [95% CI, 0.50-0.56]; PROTECHT, 0.58 [95% CI, 0.56-0.61]; CONKO, 0.54 [95% CI, 0.51-0.57]; COMPASS-CAT, 0.50 [95% CI, 0.47-0.53]; CAT Score, 0.65 [95% CI, 0.62-0.67]; EHR-CAT, 0.55 [95% CI, 0.52-0.57]). Overall, we observed a poor to modest discriminatory performance of the RAMs in our contemporary cohort of patients with cancer, with the CAT Score performing best among all evaluated scores.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3340-3349"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673340","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}

引用次数: 0

Throwing the microbiome out with the bathwater. 把微生物群和洗澡水一起倒掉。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-08 DOI: 10.1182/bloodadvances.2025016205

Marcus Geer, Mary Riwes

引用次数: 0

A common TBP-binding site mutation elevates fetal hemoglobin levels by competitive globin switching change in β-thalassemia. 在β-地中海贫血中，常见的tbp结合位点突变通过竞争性珠蛋白转换改变而升高γ-珠蛋白水平。

IF 7.4 1区医学

Blood advances Pub Date : 2025-07-08 DOI: 10.1182/bloodadvances.2024013695

Mengyang Song, Xiaolei Wei, Hualei Luo, Jueheng Wang, Yuhua Ye, Lang Qin, Chao Niu, Yong Long, Xingmin Wang, Congwen Shao, Miao Yu, Feng Gu, Xinhua Zhang, Xiangmin Xu

{"title":"A common TBP-binding site mutation elevates fetal hemoglobin levels by competitive globin switching change in β-thalassemia.","authors":"Mengyang Song, Xiaolei Wei, Hualei Luo, Jueheng Wang, Yuhua Ye, Lang Qin, Chao Niu, Yong Long, Xingmin Wang, Congwen Shao, Miao Yu, Feng Gu, Xinhua Zhang, Xiangmin Xu","doi":"10.1182/bloodadvances.2024013695","DOIUrl":"10.1182/bloodadvances.2024013695","url":null,"abstract":"Abstract: β-Thalassemia is a common monogenic disorder caused by genetic defects in β-globin genes (HBB) resulting in imbalanced synthesis of α-/β-globin and ineffective erythropoiesis. It has been well documented that patients with β-thalassemia, or even carriers, mostly experience reactivation of fetal hemoglobin (Hb F), but its underlying mechanisms are incompletely understood. We took advantage of a previously established cohort of 1142 patients with β-thalassemia with diverse thalassemic mutations subjected to targeted next-generation sequencing. Genotype-phenotype association studies demonstrated that the HBB:c.-78A>G had a remarkable effect on the elevation of Hb F levels compared with other β-thalassemic mutations. To experimentally validate this conclusion, the ribonucleoprotein transfection complex through homology-directed repair by electroporation was performed, from which we observed a consistent increase of Hb F expression in both HUDEP-2 and primary CD34+ cell lines. Furthermore, chromatin immunoprecipitation-quantitative polymerase chain reaction, dual-luciferase reporter assay, and circular chromosome conformation capture (4C) assays validated a decreased occupancy of the HBB TATA box by TATA-binding protein (TBP), leading to boosted expression of γ-globin genes by enhanced interaction between locus control regions (LCRs) and γ-globin gene promoters. The patient-based investigation and experimental validations presented in this study might lead to a better understanding of stage-specific globin-gene expression mediated by competitive binding of distal enhancers (LCRs).","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3159-3169"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802520","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}

引用次数: 0