British Journal of Haematology最新文献_第3页

Polarised dysplastic basophils in a TP53-mutated acute myeloid leukaemia tp53突变的急性髓性白血病中极化发育不良的嗜碱性粒细胞。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-08-02 DOI: 10.1111/bjh.70702

Quentin Amiot, Clara Assadi-Gazvini, Jean Maillot, Sarah Bugier, Xavier Phina-Ziebin, Carine Hejl

引用次数: 0

Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies 红线和绿灯：基因治疗遗传性红系疾病超越血红蛋白病。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-07-14 DOI: 10.1111/bjh.70675

Gaurav Joshi, Nandakumar Natarajan, Kathryn E. Dickerson, Richard A. Voit

{"title":"Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies","authors":"Gaurav Joshi, Nandakumar Natarajan, Kathryn E. Dickerson, Richard A. Voit","doi":"10.1111/bjh.70675","DOIUrl":"10.1111/bjh.70675","url":null,"abstract":"Gene therapy is revolutionizing treatment paradigms for inherited haematological and immunological conditions. Recent successes, including the United States Food and Drug Administration (FDA) approval of gene therapy products for sickle cell disease and beta-thalassaemia, highlight the translational path of gene therapies for erythroid-specific disorders. In contrast, gene therapy development for other inherited erythroid disorders remains largely preclinical. Here, we examine the emerging landscape of gene therapies for inherited non-haemoglobinopathy erythroid disorders, focusing on the status of gene therapies for Diamond–Blackfan anaemia (DBA), pyruvate kinase deficiency (PKD), X-linked sideroblastic anaemia (XLSA), congenital erythropoietic porphyria (CEP) and congenital dyserythropoietic anaemia (CDA). We discuss the latest cellular engineering approaches being applied to developing therapies for these erythroid disorders and evolving strategies for conditioning and engraftment of modified cells. Despite the rarity of these disorders individually, several convergent biological and translational themes have emerged. Leveraging shared insights across diseases may accelerate clinical translation and broaden the curative potential of gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1469-1481"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

B-cell activating factor receptor expression in B-lymphoblastic leukaemia: Flow cytometric analysis and implications for targeted therapy b淋巴细胞白血病中b细胞活化因子受体的表达：流式细胞术分析和靶向治疗的意义。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-07-24 DOI: 10.1111/bjh.70708

Parastou Tizro, Ibrahim Aldoss, Xiuli Wang, Larry W. Kwak, Zhenyuan Dong, Kevin Arango, Michael Palmer, Soungchul Cha, Jessica Hughes, Huiyan Ma, Vinod Pullarkat, Elizabeth Budde, Guido Marcucci, Winston Lee, Lorinda Soma, Stephen Forman, Joo Y. Song

{"title":"B-cell activating factor receptor expression in B-lymphoblastic leukaemia: Flow cytometric analysis and implications for targeted therapy","authors":"Parastou Tizro, Ibrahim Aldoss, Xiuli Wang, Larry W. Kwak, Zhenyuan Dong, Kevin Arango, Michael Palmer, Soungchul Cha, Jessica Hughes, Huiyan Ma, Vinod Pullarkat, Elizabeth Budde, Guido Marcucci, Winston Lee, Lorinda Soma, Stephen Forman, Joo Y. Song","doi":"10.1111/bjh.70708","DOIUrl":"10.1111/bjh.70708","url":null,"abstract":"<div>\u0000 \u0000 Cluster of differrentiation 19 (CD19)-directed therapies have significantly improved outcomes in B-cell malignancies; however, relapse driven by antigen escape remains a major clinical challenge, underscoring the need for alternative therapeutic targets. The B-cell activating factor receptor (BAFF-R), a key regulator of B-cell survival, is highly expressed in mature B-cell neoplasms, but its relevance in B-lymphoblastic leukaemia (B-ALL) remains unclear. We assessed BAFF-R expression in diagnostic and relapsed fresh B-ALL samples using multi-parameter flow cytometry. BAFF-R was consistently expressed in most cases, albeit at lower levels than in mature B cells, and expression was retained in the majority of CD19-negative relapses following CD19-directed therapy. Notably, tumor protein p53 (TP53) alterations were significantly enriched in CD19-negative immune escape disease (68.8% vs. 21.7%; p = 0.0006; OR = 7.9), yet BAFF-R expression remained preserved in this high-risk group. These findings establish BAFF-R as a stable immunotherapeutic target in B-ALL, including in CD19-negative and TP53-altered relapsed disease, and underscore its relevance amid ongoing early-phase clinical trials of BAFF-R–directed chimeric antigen receptor (CAR) T-cell therapy.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1530-1537"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The diagnosis and management of primary mediastinal B-cell lymphoma: A British Society for Haematology guideline 原发性纵隔b细胞淋巴瘤的诊断和治疗：英国血液学学会指南。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-08-23 DOI: 10.1111/bjh.70768

Wendy Osborne, Hannah Bielby, Kate Cwynarski, Dima El-Sharkawi, George Petrides, Timothy Illidge, N. George Mikhaeel, Cathy Burton, Amos Burke, Mary Gleeson, Christopher P. Fox, Andrew Davies, the BSH Committee

{"title":"The diagnosis and management of primary mediastinal B-cell lymphoma: A British Society for Haematology guideline","authors":"Wendy Osborne, Hannah Bielby, Kate Cwynarski, Dima El-Sharkawi, George Petrides, Timothy Illidge, N. George Mikhaeel, Cathy Burton, Amos Burke, Mary Gleeson, Christopher P. Fox, Andrew Davies, the BSH Committee","doi":"10.1111/bjh.70768","DOIUrl":"10.1111/bjh.70768","url":null,"abstract":"Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathological entity within the spectrum of aggressive B-cell lymphomas, characterised by unique clinical, immunophenotypic and molecular features. Since publication of the 2019 British Society for Haematology (BSH) Good Practice Paper, there have been important advances in imaging, radiotherapy approaches and systemic therapies, including chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint inhibition. Key updates include the use of PET-adapted approaches to guide radiotherapy decisions following first-line chemoimmunotherapy, with omission of consolidative radiotherapy in patients achieving complete metabolic response. The guideline emphasises the importance of dose-intensive chemoimmunotherapy regimens and provides a framework for the clinical management of patients with Deauville stage 4 (DS4) and DS5 response status on PET-CT imaging following chemoimmunotherapy.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1505-1517"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.70768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Integrating novel therapeutic strategies in myeloproliferative neoplasms: Driving disease-directed progress 整合骨髓增殖性肿瘤的新治疗策略：推动疾病导向的进展。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-07-09 DOI: 10.1111/bjh.70672

Trung Q. Ngo, Maria Georgiou, Donal P. McLornan, Claire N. Harrison

{"title":"Integrating novel therapeutic strategies in myeloproliferative neoplasms: Driving disease-directed progress","authors":"Trung Q. Ngo, Maria Georgiou, Donal P. McLornan, Claire N. Harrison","doi":"10.1111/bjh.70672","DOIUrl":"10.1111/bjh.70672","url":null,"abstract":"Over the past decade, there has been a substantial increase in the diversity and number of therapeutic options for myeloproliferative neoplasms (MPNs). While many remain within the clinical trial arena, the clinician and patient community have seen more approvals reaching the clinic and a rethink on how best we should be approaching these disorders is required. In parallel, there needs to be a paradigm shift in end-point considerations within MPN clinical trial design, with a growing emphasis on longer term disease stability and modification, molecular responses, histomorphological modification, reductions in complications (e.g. thrombotic complications or disease transformation) and improved survival alongside the conventional goals such as haematological responses and symptom and spleen improvements where relevant. Given the heterogeneity of these disorders, with often marked intrapatient variability, greater consideration must be given to optimised sequencing strategies and rational combination approaches and, importantly, an emphasis on patient-specific trajectories. In this review, we appraise the contemporary therapeutic armamentarium across the MPN spectrum and explore how these advances may best facilitate increasing personalised approaches in an evolving and complex treatment landscape.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1450-1468"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.70672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pathway alteration burden derived from whole-exome sequencing is associated with survival in primary central nervous system lymphoma 来自全外显子组测序的通路改变负担与原发性中枢神经系统淋巴瘤的生存率相关。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-08-15 DOI: 10.1111/bjh.70734

Jiajun Gui, Apeng Yang, Junfang Lin, Qincheng Che, Lin Feng, Ping Lin, Junmin Chen, Zhiyong Zeng

{"title":"Pathway alteration burden derived from whole-exome sequencing is associated with survival in primary central nervous system lymphoma","authors":"Jiajun Gui, Apeng Yang, Junfang Lin, Qincheng Che, Lin Feng, Ping Lin, Junmin Chen, Zhiyong Zeng","doi":"10.1111/bjh.70734","DOIUrl":"10.1111/bjh.70734","url":null,"abstract":"<div>\u0000 \u0000 Primary central nervous system lymphoma (PCNSL) exhibits marked clinical heterogeneity, while genomic risk stratification remains largely gene-centric. The prognostic relevance of cumulative pathway-level alterations remains unclear. Whole-exome sequencing was performed in 76 newly diagnosed PCNSL patients treated with programmed cell death protein 1 (PD-1) inhibitor–based immunochemotherapy. Somatic mutations were mapped to 10 canonical oncogenic pathways, and pathway disruption was quantified using the number of pathway alterations (NPAs). Associations with clinical, genomic and survival outcomes were evaluated. Frequent alterations were observed in the Notch, receptor tyrosine kinase–RAS (RTK–RAS), Hippo and Wingless-related integration site (Wnt) pathways. NPA showed substantial interindividual variability and was strongly correlated with tumour mutational burden but only weakly associated with fraction of genome altered. Higher NPA was associated with distinct systemic inflammatory features and inferior overall and progression-free survival. In multivariable analyses adjusting for International Extranodal Lymphoma Study Group (IELSG) score and LymphGen subtype, NPA remained independently associated with both overall survival (hazard ratio [HR] 1.26, p = 0.025) and progression-free survival (HR 1.24, p = 0.029). Notch pathway alterations were associated with inferior survival and higher pathway activity scores. Pathway-level mutational burden captures clinically relevant genomic heterogeneity and may serve as a prognostic biomarker in PCNSL.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1518-1529"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multiparameter flow cytometry versus droplet digital polymerase chain reaction for monitoring measurable residual disease in paediatric fusion gene-positive acute myeloid leukaemia 多参数流式细胞术与液滴数字聚合酶链反应监测儿童融合基因阳性急性髓性白血病可测量的残留疾病。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-08-11 DOI: 10.1111/bjh.70714

Rongrong Liu, Bing Li, Jingying Zhang, Weiqun Xu, Fenying Zhao, Juan Liang, Diying Shen, Yi Zheng, Ruiqi Tang, Yongmin Tang, Xiaojun Xu

{"title":"Multiparameter flow cytometry versus droplet digital polymerase chain reaction for monitoring measurable residual disease in paediatric fusion gene-positive acute myeloid leukaemia","authors":"Rongrong Liu, Bing Li, Jingying Zhang, Weiqun Xu, Fenying Zhao, Juan Liang, Diying Shen, Yi Zheng, Ruiqi Tang, Yongmin Tang, Xiaojun Xu","doi":"10.1111/bjh.70714","DOIUrl":"10.1111/bjh.70714","url":null,"abstract":"<div>\u0000 \u0000 Measurable residual disease (MRD) monitoring is crucial for prognostic stratification in paediatric acute myeloid leukaemia (AML). This study compared the performance of multiparameter flow cytometry (MFC) and droplet digital polymerase chain reaction (ddPCR) for MRD assessment in 116 paediatric AML patients at end of induction (EOI)-1, EOI-2 and end of consolidation (EOC)-1. Compared to MFC, ddPCR revealed a significantly slower rate of MRD negativity conversion, with moderate concordance between methods. Both MFC and ddPCR were significant predictors of 5-year event-free survival (EFS) at EOIs. For instance, MFC-MRD ≥1% at EOI-1 was associated with a 5-year EFS of 50.2 ± 19.8% vs. 79.4 ± 6.4% for patients with MRD <1% (p = 0.003), while corresponding ddPCR rates were 41.0 ± 23.8% vs. 91.7 ± 4.5% (p < 0.001). Notably, the prognostic power of MFC diminished at EOC-1, while ddPCR remained significant. Subgroup analysis by genetic alterations revealed that ddPCR provided significant prognostic stratification across all genetic subgroups while MFC did not. Combining both methods yielded improved risk discrimination. Patients with double positive MRD presented very low survival rates either at EOI-1, EOI-2 and EOC-1. In conclusion, ddPCR offers higher sensitivity and sustained prognostic performance, whereas MFC remains a practical front-line tool; integrating the two methods enables more precise risk stratification.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1562-1573"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multiomics analysis focusing on genome-wide DNA methylation in paediatric acute promyelocytic leukaemia 儿童急性早幼粒细胞白血病基因组DNA甲基化的多组学分析。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-08-10 DOI: 10.1111/bjh.70733

Etsuko Murayama, Tomoko Kawai, Genki Yamato, Norio Shiba, Kentaro Ohki, Yusuke Hara, Taeko Kaburagi, Takumi Takizawa, Hirohide Kawasaki, Kenichi Yoshida, Yasuhito Nannya, Daisuke Tomizawa, Takashi Taga, Souichi Adachi, Yuki Yuza, Hiroyuki Takahashi, Seishi Ogawa, Yasuhide Hayashi

{"title":"Multiomics analysis focusing on genome-wide DNA methylation in paediatric acute promyelocytic leukaemia","authors":"Etsuko Murayama, Tomoko Kawai, Genki Yamato, Norio Shiba, Kentaro Ohki, Yusuke Hara, Taeko Kaburagi, Takumi Takizawa, Hirohide Kawasaki, Kenichi Yoshida, Yasuhito Nannya, Daisuke Tomizawa, Takashi Taga, Souichi Adachi, Yuki Yuza, Hiroyuki Takahashi, Seishi Ogawa, Yasuhide Hayashi","doi":"10.1111/bjh.70733","DOIUrl":"10.1111/bjh.70733","url":null,"abstract":"<div>\u0000 \u0000 We conducted a multiomics analysis of paediatric acute promyelocytic leukaemia (APL) in 36 patients enrolled in the Japanese AML-P05 study. Targeted deep sequencing identified EP300 mutations (n = 2) and MYC-internal tandem duplication (ITD) (n = 1), which have not been previously reported in APLs. DNA methylation analysis classified 34 paediatric APLs into two groups: hypermethylation and hypomethylation. Patients in the hypermethylation group had significantly worse outcomes compared to those in the hypomethylation group (3-year overall survival: 80% vs. 100%, p = 0.043; 3-year event-free survival: 73% vs. 95%, p = 0.049). Remarkably, the EBF1-binding motif was enriched in 82.3% of the CpG sites that were differentially methylated between the hyper- and hypomethylation groups, and these sites were predominantly located in enhancer regions. Among the 1427 genes that were significantly differentially expressed between the two groups, EP300 was significantly downregulated in the hypermethylation group. Pathway analyses revealed global transcriptional downregulation in the hypermethylation group; however, MYC, a known EP300-repressed gene, was upregulated within the G2M checkpoint. Our findings suggest a potential link among enhancer-based epigenetic dysregulation involving DNA methylation at EBF1-binding sites, EP300 dysfunction and MYC activation. These alterations may contribute to disease heterogeneity and prognosis in paediatric APL.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 4","pages":"1586-1597"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

From haemostasis to immunity: The expanding frontiers of platelet biology 从止血到免疫：血小板生物学不断拓展的前沿。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-07-25 DOI: 10.1111/bjh.70710

Xun Grace Wu, Nicole Tomei, Heyu Ni

引用次数: 0

Hereditary antithrombin deficiency in pregnancy 简要回顾妊娠遗传性抗凝血酶缺乏症。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-10-16 Epub Date: 2026-07-29 DOI: 10.1111/bjh.70716

Oluwatosin Afolabi, Samuel Ruder, Maria T. DeSancho

引用次数: 0