British Journal of Haematology最新文献_第10页

The myeloid cell leukaemia-1 inhibitor MIK665 is a potent therapy in preclinical models of paediatric acute myeloid leukaemia 髓细胞白血病-1抑制剂MIK665是一种有效的治疗儿科急性髓细胞白血病的临床前模型。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-04 DOI: 10.1111/bjh.70596

Patrick Connerty, John N. Colgan, Fatima El-Najjar, Emma Henry, Jinhan Xie, Dana Idais, Carmine Gentile, Jie Mao, M. Emmy M. Dolman, Glenn M. Marshall, Richard B. Lock

{"title":"The myeloid cell leukaemia-1 inhibitor MIK665 is a potent therapy in preclinical models of paediatric acute myeloid leukaemia","authors":"Patrick Connerty, John N. Colgan, Fatima El-Najjar, Emma Henry, Jinhan Xie, Dana Idais, Carmine Gentile, Jie Mao, M. Emmy M. Dolman, Glenn M. Marshall, Richard B. Lock","doi":"10.1111/bjh.70596","DOIUrl":"10.1111/bjh.70596","url":null,"abstract":"<div>\u0000 \u0000 Paediatric acute myeloid leukaemia (AML) remains a deadly disease, with survival rates reaching a plateau despite treatment with high-intensity chemotherapy. Recent advancements in therapeutic strategies, such as targeted therapies to inhibit AML dependencies, have aimed to improve outcomes. The evasion of apoptosis, regulated by the B-cell lymphoma 2 (BCL2) family of proteins, is a key feature of cancer progression and treatment resistance. Bcl-2 homology domain 3 (BH3) mimetics, such as venetoclax (ABT-199), which targets BCL2, have shown promising activity in AML. This study investigates for the first time the therapeutic potential of MIK665, a BH3 mimetic targeting myeloid cell leukaemia-1 (MCL1), in paediatric AML. We evaluated the efficacy of MIK665 against a diverse panel of AML cell lines and demonstrated its effectiveness as a single-agent treatment. Additionally, MIK665 showed significant activity against a subset of paediatric AML patient-derived xenografts (PDXs) in both ex vivo and in vivo experiments, with minimal impact on cardiac tissue pathophysiology. These findings strongly support the clinical advancement of MIK665 for paediatric AML treatment in a precision medicine approach.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"491-502"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154416","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

Foamy cell infiltration as a morphological challenge: Histiocytosis versus plasma cell neoplasm 泡沫细胞浸润作为形态学挑战：组织细胞增生与浆细胞肿瘤。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-04 DOI: 10.1111/bjh.70546

Carmen Rodriguez-Miñón, Alberto Lázaro-García, Francesca Guijarro, Sandra Castaño-Díez, Cecilia Grandi, Jose R. Álamo

引用次数: 0

Diagnosis and management of neutropenia in adults: Expert guidance 成人中性粒细胞减少症的诊断和治疗：专家指导。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-29 DOI: 10.1111/bjh.70640

Karl Welte, Cornelia Zeidler, Julia Skokowa, Sabine Mellor-Heineke, Audrey Anna Bolyard, David Dale

{"title":"Diagnosis and management of neutropenia in adults: Expert guidance","authors":"Karl Welte, Cornelia Zeidler, Julia Skokowa, Sabine Mellor-Heineke, Audrey Anna Bolyard, David Dale","doi":"10.1111/bjh.70640","DOIUrl":"10.1111/bjh.70640","url":null,"abstract":"Neutropenia in general is defined as a blood neutrophil count of less than 1.5 × 109/L, in severe neutropenia counts drop to less than 0.5 × 109/L, but the definition of neutropenia varies according to the patient's ethnic origin and age. For Caucasian adults, the absolute neutrophil count (ANC) threshold of 1.8 × 109/L is adopted for the definition of neutropenia according to the World Health Organization (see Fioredda et al. (1)). It can be inherited or acquired, and it is an uncommon haematological finding in adult outpatient clinics. Neutropenia can result from decreased production of neutrophil precursors in the bone marrow, as in the case of severe congenital neutropenia, or from increased utilization of neutrophils in some bacterial infections, or accelerated destruction as is the case with drug-induced neutropenia, viral infections and autoimmune neutropenia. Severe chronic neutropenia increases susceptibility to bacterial or fungal infections. Treating severe chronic neutropenia patients with granulocyte colony-stimulating factor (G-CSF) can increase neutrophil counts for most types of neutropenia. This article will provide guidance on diagnosing and managing severe chronic neutropenia in adult patients and provides a transition programme from adolescence to adulthood.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"432-440"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.70640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343453","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

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers. 多发性骨髓瘤的骨进展：唑来膦酸对至少达到非常好的部分缓解的患者的益处和骨转换标志物的预后价值。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 DOI: 10.1111/bjh.70612

Michael Tveden Gundesen, Annette Juul Vangsted, Carsten Helleberg, Einar Haukås, Trine Silkjær, Jonna Skov Madsen, Jon Thor Asmussen, Elena Manuela Teodorescu, Bo Amdi Jensen, Tobias Schmidt Slørdahl, Aneta Alexandra Nielsen, Dorte Aalund Olsen, Kent Søe, Hareth Nahi, Anders Waage, Niels Abildgaard, Fredrik Schjesvold, Thomas Lund

{"title":"Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.","authors":"Michael Tveden Gundesen, Annette Juul Vangsted, Carsten Helleberg, Einar Haukås, Trine Silkjær, Jonna Skov Madsen, Jon Thor Asmussen, Elena Manuela Teodorescu, Bo Amdi Jensen, Tobias Schmidt Slørdahl, Aneta Alexandra Nielsen, Dorte Aalund Olsen, Kent Søe, Hareth Nahi, Anders Waage, Niels Abildgaard, Fredrik Schjesvold, Thomas Lund","doi":"10.1111/bjh.70612","DOIUrl":"https://doi.org/10.1111/bjh.70612","url":null,"abstract":"The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2 years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2 years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4 years. Continued monthly ZOL beyond 2 years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (≥0.30 μg/L) and TRAcP (≥4 U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2 years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710799","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

Improvements over time in survival after post-transplant relapse of adult T-cell leukaemia/lymphoma and trends of salvage therapy in a real-world experience 成人t细胞白血病/淋巴瘤移植后复发的生存率随时间的提高和现实世界经验中挽救治疗的趋势

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-15 DOI: 10.1111/bjh.70631

Hidehiro Itonaga, Takuya Fukushima, Koji Kato, Hiroyuki Muranushi, Masahito Tokunaga, Takayoshi Miyazono, Ayumu Ito, Tetsuya Eto, Youko Suehiro, Takeharu Kato, Machiko Fujioka, Toshiro Kawakita, Naoyuki Uchida, Yasuo Mori, Makoto Yoshimitsu, Hirohisa Nakamae, Kazuho Morichika, Kenji Ishitsuka, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Shigeo Fuji, ATL working groups of the Japanese Society for Transplantation and Cellular Therapy

{"title":"Improvements over time in survival after post-transplant relapse of adult T-cell leukaemia/lymphoma and trends of salvage therapy in a real-world experience","authors":"Hidehiro Itonaga, Takuya Fukushima, Koji Kato, Hiroyuki Muranushi, Masahito Tokunaga, Takayoshi Miyazono, Ayumu Ito, Tetsuya Eto, Youko Suehiro, Takeharu Kato, Machiko Fujioka, Toshiro Kawakita, Naoyuki Uchida, Yasuo Mori, Makoto Yoshimitsu, Hirohisa Nakamae, Kazuho Morichika, Kenji Ishitsuka, Junya Kanda, Takahiro Fukuda, Yoshiko Atsuta, Shigeo Fuji, ATL working groups of the Japanese Society for Transplantation and Cellular Therapy","doi":"10.1111/bjh.70631","DOIUrl":"10.1111/bjh.70631","url":null,"abstract":"<div>\u0000 \u0000 Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers potentially curative outcomes for adult T-cell leukaemia/lymphoma (ATL), but post-transplant refractory/relapsed (R/R) ATL is associated with poor outcomes. Advances have been made in transplant modalities, novel targeted agents and supportive care; however, it remains unclear whether these advances have improved survival outcomes of post-transplant R/R ATL. To clarify changes in survival after post-transplant R/R, we evaluated the survival outcomes in 1146 patients over a 24-year period, using a nationwide database. The period was divided into three groups: 1999–2010 (early period, as reference), 2011–2016 (middle period) and 2017–2022 (late period). In patients with refractory ATL, multivariate analyses showed no significant difference in overall mortality (OM) after post-transplant refractory in the early and middle periods, but a significantly lower OM in the late period than in the early period (hazard ratio [HR], 0.73 [95% confidence interval, 0.55–0.96]). In patients with relapsed ATL, OM after post-transplant relapse was significantly lower in the middle (HR 0.62 [0.48–0.80]) and late periods (HR 0.68 [0.52–0.90]) than in the early period. Thus, recent advances appear to have contributed to increased opportunities for therapeutic interventions, leading to improved survival outcomes in patients with post-transplant R/R ATL.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"544-556"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256606","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

Metabolic heterogeneity-based radiomic model predicts treatment outcomes of primary mediastinal B-cell lymphoma patients in the IELSG37 study 在IELSG37研究中，基于代谢异质性的放射组学模型预测原发性纵隔b细胞淋巴瘤患者的治疗结果。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-16 DOI: 10.1111/bjh.70614

L. Ceriani, L. Milan, L. Cascione, A. Di Rocco, I. Kryachok, A. J. Davies, A. Stathis, D. Rossi, P. W. M. Johnson, M. Martelli, E. Zucca

{"title":"Metabolic heterogeneity-based radiomic model predicts treatment outcomes of primary mediastinal B-cell lymphoma patients in the IELSG37 study","authors":"L. Ceriani, L. Milan, L. Cascione, A. Di Rocco, I. Kryachok, A. J. Davies, A. Stathis, D. Rossi, P. W. M. Johnson, M. Martelli, E. Zucca","doi":"10.1111/bjh.70614","DOIUrl":"10.1111/bjh.70614","url":null,"abstract":"Early identification of patients at risk of failing first-line therapy remains a key challenge in primary mediastinal B-cell lymphoma (PMBCL). This study assessed whether positron emission tomography (PET) radiomics could predict treatment outcomes in PMBCL. Baseline PET/computed tomography (CT) scans from 501 patients enrolled in the International Extranodal Lymphoma Study Group 37 (IELSG37) trial and treated with rituximab- and doxorubicin-based immunochemotherapy were analysed. Functional PET parameters reflecting tumour burden (metabolic tumour volume, MTV), glucose consumption (total lesion glycolysis, TLG) and metabolic heterogeneity (MH) were calculated using a 25% maximum standard uptake value (SUVmax) segmentation threshold. Radiomic analysis was performed in 495 patients, extracting 107 features; 74 features uncorrelated with SUVmax and MTV were selected and analysed using a recursive-partitioning classification tree (Ctree) approach. Ctree identified grey-level run-length matrix run variance (GLRLM-RV), a marker of MH, as the most significant prognostic feature. Patients with low MH (GLRLM-RV <0.136) had a 5-year progression-free survival (PFS) of 93%, compared with 65% in those with high MH (p < 0.0001). Five-year overall survival (OS) was 96% vs. 80% respectively (p < 0.0001). A subsequent Ctree model integrating GLRLM-RV and TLG further improved prognostic stratification for PFS and OS (p < 0.0001), outperforming established prognostic indices (International Prognostic Index [IPI], revised-IPI and age-adjusted IPI).","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"514-523"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.70614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262175","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

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 : 2026-08-11 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":"https://doi.org/10.1111/bjh.70714","url":null,"abstract":"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.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","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

Concurrent antiviral–immunochemotherapy strategy safely overcomes high hepatitis B viral load barrier in diffuse large B-cell lymphoma: A multicentre cohort study 在弥漫性大B细胞淋巴瘤中，同步抗病毒免疫化疗策略可安全克服高乙肝病毒载量屏障：一项多中心队列研究

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-02 DOI: 10.1111/bjh.70584

Yuxiao Zhao, Jingjing Guo, Xiran Wang, Lei Cao, Yi Xia, Haorui Shen, Ran Li, Ping Wu, Hongling Mi, Jing Zhang, Jianyong Li, Hailing Liu, Xiaoyan Qu, Lei Fan

{"title":"Concurrent antiviral–immunochemotherapy strategy safely overcomes high hepatitis B viral load barrier in diffuse large B-cell lymphoma: A multicentre cohort study","authors":"Yuxiao Zhao, Jingjing Guo, Xiran Wang, Lei Cao, Yi Xia, Haorui Shen, Ran Li, Ping Wu, Hongling Mi, Jing Zhang, Jianyong Li, Hailing Liu, Xiaoyan Qu, Lei Fan","doi":"10.1111/bjh.70584","DOIUrl":"10.1111/bjh.70584","url":null,"abstract":"<div>\u0000 \u0000 Although antiviral prophylaxis is standard for lymphoma patients with chronic hepatitis B virus (HBV) infection to prevent HBV reactivation (HBVr), the optimal timing for high-risk patients (baseline HBV deoxyribonucleic acid (DNA) ≥4 log10 IU/mL) during immunochemotherapy remains unclear. A multicentre retrospective study analysed 112 chronic HBV patients among 1120 newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients, stratified by baseline viral load (low: <104 IU/mL, n = 82; high: ≥104 IU/mL, n = 30). We assessed antiviral timing, virological dynamics and clinical outcomes. Antivirals (mainly entecavir) suppressed HBV DNA to undetectable levels in high-load patients (median start 1.65 × 106 IU/mL; p = 0.001). The 3-year cumulative HBVr rates were low (4.2% overall; 4.5% high vs. 4.1% low load, p = 0.955), with one fatal HBVr after discontinuation. Liver toxicity was mild (grade 1–2 transaminase elevations: 33.3%–36.7%). High and low viral load groups achieved comparable 3-year progression-free survival (80.9% vs. 70.6%, p = 0.137), overall response rates (86.7% vs. 82.9%) and complete remission rates (70.0% vs. 64.6%). Propensity score-matched analysis confirmed no significant differences in progression-free survival or HBVr. Concurrent initiation of antiviral prophylaxis with immunochemotherapy is safe and effective, preventing HBVr and enabling timely immunochemotherapy in DLBCL patients with high HBV DNA levels.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"503-513"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142218","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

Evolution of the drug sensitivity landscape of chronic lymphocytic leukaemia 慢性淋巴细胞白血病药物敏感性格局的演变。

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-06-10 DOI: 10.1111/bjh.70603

Johanne U. Hermansen, Yanping Yin, Geir E. Tjønnfjord, Anthony R. Mato, Sigrid S. Skånland

{"title":"Evolution of the drug sensitivity landscape of chronic lymphocytic leukaemia","authors":"Johanne U. Hermansen, Yanping Yin, Geir E. Tjønnfjord, Anthony R. Mato, Sigrid S. Skånland","doi":"10.1111/bjh.70603","DOIUrl":"10.1111/bjh.70603","url":null,"abstract":"<div>\u0000 \u0000 Targeted therapies have transformed modern management of chronic lymphocytic leukaemia (CLL). Still, CLL remains an incurable disease, and key unresolved challenges include development of treatment resistance and intolerance. To address these challenges, it is necessary to define clinically actionable biomarkers that can predict individual treatment responses. Here, we aimed to map the treatment sensitivity and resistance landscapes of CLL cells from treatment-naïve and treatment-exposed patients to understand the evolution of treatment vulnerabilities. We performed ex vivo drug screens with 94 single agents and 87 drug combinations on CLL cells from treatment-naïve, ibrutinib-exposed or idelalisib-exposed patients. We found that overall drug sensitivity was reduced in cells from patients who had received treatment. Specifically, sensitivity to B-cell lymphoma 2 (Bcl-2) inhibitors was significantly reduced in both ibrutinib-exposed and idelalisib-exposed patient cells. Furthermore, combined Bruton's tyrosine kinase inhibitor (BTK)/Bcl-2 inhibition became less relevant in advanced disease, while dual mitogen-activated protein kinase kinase (MEK)/Bcl-2 inhibition was identified as an effective new treatment modality. Our findings provide valuable insights that may assist clinical decisions regarding treatment sequencing and treatment options for relapsed/refractory disease.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"469-479"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.70603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209371","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

Identification of GSE1 as a PAX5 fusion partner and characterization of PAX5 fusion signature in B-cell acute lymphoblastic leukaemia b细胞急性淋巴细胞白血病中GSE1作为PAX5融合伴侣的鉴定及PAX5融合特征的表征

IF 3.6 2区医学

British Journal of Haematology Pub Date : 2026-08-11 Epub Date: 2026-05-27 DOI: 10.1111/bjh.70578

Haina Wang, Jingjing Xue, Wenli Yan, Yuan Gao, Xin Zong, Dong Zhou, Dan Huang, Hongchen Liu, Xuehong Zhang, Jinsong Yan

{"title":"Identification of GSE1 as a PAX5 fusion partner and characterization of PAX5 fusion signature in B-cell acute lymphoblastic leukaemia","authors":"Haina Wang, Jingjing Xue, Wenli Yan, Yuan Gao, Xin Zong, Dong Zhou, Dan Huang, Hongchen Liu, Xuehong Zhang, Jinsong Yan","doi":"10.1111/bjh.70578","DOIUrl":"10.1111/bjh.70578","url":null,"abstract":"<div>\u0000 \u0000 In B-cell acute lymphoblastic leukaemia (B-ALL), paired box 5 (PAX5) rearrangement (PAX5-r) represents a critical genetic driver. Here, we report the identification of an in-frame PAX5::GSE1 fusion gene in a patient with B-ALL. Functional characterization revealed that the PAX5::GSE1 protein localizes to the nucleus, promotes cell proliferation and suppresses wild-type PAX5 transcriptional activity. Notably, its transcript levels correlated with treatment response, supporting its utility as a minimal residual disease biomarker. By analysing 330 patients with PAX5-r B-ALL, we identified 76 distinct in-frame partner genes and delineated their breakpoint characteristics. Integrated multi-cohort transcriptomic analysis further revealed that PAX5-r induces a convergent expression profile relative to healthy individuals, characterized by dysregulation of the retinoblastoma transcriptional corepressor 1 (RB1) and p53 pathways and overexpression of nucleophosmin 1 (NPM1). These findings help to clarify core molecular mechanisms underlying PAX5-r-driven leukaemogenesis and highlight potential therapeutic vulnerabilities.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"209 2","pages":"480-490"},"PeriodicalIF":3.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040486","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