Haematologica最新文献

Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension. 治疗性Fc融合因子VIII与中性pH下新生儿Fc受体的结合与半衰期延长不良相关。

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2024-12-12 DOI: 10.3324/haematol.2024.286536

Alejandra Reyes-Ruiz, Sandrine Delignat, Aishwarya Sudam Bhale, Victoria Daventure, Robin V Lacombe, Leslie Dourthe, Olivier Christophe, Sune Justesen, Krishnan Venkataraman, Jordan D Dimitrov, Sebastien Lacroix-Desmazes

{"title":"Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension.","authors":"Alejandra Reyes-Ruiz, Sandrine Delignat, Aishwarya Sudam Bhale, Victoria Daventure, Robin V Lacombe, Leslie Dourthe, Olivier Christophe, Sune Justesen, Krishnan Venkataraman, Jordan D Dimitrov, Sebastien Lacroix-Desmazes","doi":"10.3324/haematol.2024.286536","DOIUrl":"10.3324/haematol.2024.286536","url":null,"abstract":"Fusion of therapeutic proteins to the Fc fragment of human immunoglobulin (Ig) G1 promotes their neonatal Fc receptor (FcRn)-mediated recycling and subsequent extension in circulating half-life. However, different Fc-fused proteins, as well as antibodies with different variable domains but identical Fc, may differ in terms of extension in half-life. Here we compared the binding behavior to FcRn of Fc-fused FVIII, Fc-fused FIX and two human monoclonal HIV-1 broadly-neutralizing IgG1, m66.6 and VRC01 with identical Fc. While all molecules bound FcRn at acidic pH, only rFVIIIFc and m66.6 interacted with FcRn at neutral pH. In silico modeling predicted a role for charged residues in the C1 and C2 domains of FVIII, and in the variable domains of m66.6, in the neutral binding to FcRn. Accordingly, mutations of key positively charged amino-acids in the FVIII C1C2 domains decreased the binding of the protein to FcRn at pH 7.4 in vitro and increased the half-life of rFVIIIFc in von Willebrand factor- knockout mice. Our findings suggest that the removal of positively charged patches on Fc-fused proteins to ameliorate FcRn recycling without affecting therapeutic efficacy, may improve their pharmacokinetic properties.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1523-1535"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812934","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

FLI1 and GATA1 govern TLN1 transcription: new insights into FLI1-related platelet disorders. FLI1和GATA1调控TLN1转录：对FLI1相关血小板疾病的新见解

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-01-02 DOI: 10.3324/haematol.2024.286372

Elisa Gabinaud, Laurent Hannouche, Mathilde Veneziano-Broccia, Johannes Van Agthoven, Justine Suffit, Julien Maurizio, Delphine Potier, Dominique Payet-Bornet, Delphine Bastelica, Elisa Andersen, Manal Ibrahim-Kosta, Timothée Bigot, Céline Falaise, Anne Vincenot, Pierre-Emmanuel Morange, Paul Saultier, Marie-Christine Alessi, Marjorie Poggi, Hemostasis Unit Of Lille

{"title":"FLI1 and GATA1 govern TLN1 transcription: new insights into FLI1-related platelet disorders.","authors":"Elisa Gabinaud, Laurent Hannouche, Mathilde Veneziano-Broccia, Johannes Van Agthoven, Justine Suffit, Julien Maurizio, Delphine Potier, Dominique Payet-Bornet, Delphine Bastelica, Elisa Andersen, Manal Ibrahim-Kosta, Timothée Bigot, Céline Falaise, Anne Vincenot, Pierre-Emmanuel Morange, Paul Saultier, Marie-Christine Alessi, Marjorie Poggi, Hemostasis Unit Of Lille","doi":"10.3324/haematol.2024.286372","DOIUrl":"10.3324/haematol.2024.286372","url":null,"abstract":"Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets. We focused on four FLI1 variants, two of which are novel: p.G307R and p.R340C. We assessed the impact of FLI1 variants on megakaryopoiesis using single-cell RNA sequencing, and defects were confirmed in patients' platelets and cell lines. Results showed variants p.R337Q, p.K345E and p.R340C exhibited faulty nuclear localization and defective transcriptional activity in vitro and variants p.K345E and p.G307R affected protein stability. A total of 626 genes were differentially expressed in patient megakaryocytes, including genes associated with the platelet activation pathway. TLN1 was among the most down-regulated genes, with an 88% reduction in talin-1 protein levels in FLI1 patients' platelets. Analysis of chromatin immunoprecipitation sequencing data revealed FLI1-binding regions in the TLN1 gene. Luciferase reporter gene assays revealed the functional role of an intronic binding region in cooperation with GATA1. FLI1 variants were linked to reduced cooperative transcriptional activity. These findings reveal novel mechanisms underlying the pathogenicity of FLI1 variants. Defective cooperation between FLI1 variants and GATA1 may play a role in talin-1 deficiency in FLI1 patients' platelets, thus contributing to platelet dysfunction. Moreover, talin-1 could serve as a biomarker for classifying the pathogenicity of FLI1 variants.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1584-1595"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914625","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

One CHiP to rule them all? Mechanistic insight into carfilzomib-induced lung injury with neutrophil extracellular trap formation following cellular immunotherapy. 一个芯片可以统治所有芯片？细胞免疫治疗后卡非佐米诱导的肺损伤与中性粒细胞胞外陷阱形成的机制。

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-02-13 DOI: 10.3324/haematol.2024.286596

Julia Katharina Scholz, Lena Stabel, Nora Rebecca Schwingen, Jasmin Knopf, Anna-Sophie Flatt, Tobias Bäuerle, Stefan Krause, Heidi Waibel, Moritz Leppkes, K Martin Kortüm, Hermann Einsele, Andreas Mackensen, Martin Herrmann, Simon Völkl, Fabian Müller

引用次数: 0

Patients with high-risk acute promyelocytic leukemia need maintenance therapy for 1 year - the PROS. 高危急性早幼粒细胞白血病患者需要一年的维持治疗。

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.3324/haematol.2025.287417

Martin S Tallman

引用次数: 0

Bispecific antibodies in follicular lymphoma. 滤泡淋巴瘤中的双特异性抗体

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2024-10-31 DOI: 10.3324/haematol.2024.285245

Imran A Nizamuddin, Nancy L Bartlett

{"title":"Bispecific antibodies in follicular lymphoma.","authors":"Imran A Nizamuddin, Nancy L Bartlett","doi":"10.3324/haematol.2024.285245","DOIUrl":"10.3324/haematol.2024.285245","url":null,"abstract":"Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm for multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at 2 years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1472-1482"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545068","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

Prognostic relevance of variant allele frequency for treatment outcomes in patients with acute myeloid leukemia: a study by the Spanish PETHEMA registry. 变异等位基因频率与急性髓性白血病患者治疗结果的预后相关性：西班牙PETHEMA登记处的一项研究。

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-02-27 DOI: 10.3324/haematol.2024.286311

Rafael Colmenares, Noemi Alvarez, Eva Barragan, Blanca Boluda, Maria J Larrayoz, Maria Carmen Chillon, Elena Soria-Saldise, Cristina Bilbao, Joaquin Sanchez-Garcia, Teresa Bernal, David Martinez-Cuadron, Cristina Gil, Josefina Serrano, Carlos Rodriguez-Medina, Juan Bergua, Jose A Perez-Simon, Maria Calbacho, Juan M Alonso-Dominguez, Jorge Labrador, Mar Tormo, Pilar Herrera-Puente, Cristina Martin-Arriscado, Andres Arroyo-Barea, Inmaculada Rapado, Claudia Sargas, Iria Vazquez, Maria J Calasanz, Teresa Gomez-Casares, Ramon Garcia-Sanz, Rebeca Rodriguez-Veiga, Joaquin Martinez-Lopez, Rosa Ayala, Pau Montesinos, Pethema Group

引用次数: 0

Lower incidence of chronic graft-versus-host disease after ruxolitinib plus extracorporeal photopheresis versus ruxolitinib alone in steroid-refractory acute graft-versus-host disease following allogeneic stem cell transplantation. 同种异体干细胞移植后类固醇难治性急性移植物抗宿主病，鲁索利替尼联合体外光移植术治疗后慢性移植物抗宿主病的发生率较单独鲁索利替尼低。

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-03-20 DOI: 10.3324/haematol.2024.286824

Iryna Lastovytska, Silke Heidenreich, Evgeny Klyuchnikov, Christian Niederwieser, Nico Gagelmann, Johanna Richter, Radwan Massoud, Kristin Rathje, Tetiana Perekhrestenko, Gaby Zeck, Catherina Lück, Dietlinde Janson, Christine Wolschke, Francis Ayuk, Nicolaus Kröger

{"title":"Lower incidence of chronic graft-versus-host disease after ruxolitinib plus extracorporeal photopheresis versus ruxolitinib alone in steroid-refractory acute graft-versus-host disease following allogeneic stem cell transplantation.","authors":"Iryna Lastovytska, Silke Heidenreich, Evgeny Klyuchnikov, Christian Niederwieser, Nico Gagelmann, Johanna Richter, Radwan Massoud, Kristin Rathje, Tetiana Perekhrestenko, Gaby Zeck, Catherina Lück, Dietlinde Janson, Christine Wolschke, Francis Ayuk, Nicolaus Kröger","doi":"10.3324/haematol.2024.286824","DOIUrl":"10.3324/haematol.2024.286824","url":null,"abstract":"We compared long-term outcomes in 78 patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) treated at the University Medical Center Hamburg, Germany, between December 2015 and August 2022 who received either ruxolitinib alone (Ruxo, N=29) or Ruxo plus extracorporeal photopheresis (Ruxo-ECP, N=49). Patients were well balanced between both arms except for SR-aGvHD grade IV which was higher in the Ruxo-ECP group (45% vs. 14%, P<0.001). In both cohorts, steroids were tapered rapidly, and median steroid treatment was 39 days in Ruxo and 35 days in Ruxo-ECP. The overall response rate including complete remissions (CR) of aGvHD at day 28 was 90% and 31% for Ruxo versus 86% and 0% (P<0.001, respectively) for Ruxo-ECP. At six months, partial remission (PR) and CR status of evaluable patients was 11% and 50% in Ruxo-ECP versus 10% and 40% after Ruxo alone, respectively (P=0.018). At 12 months, PR and CR status was 6% and 17% in the Ruxo group, but 82% and 64% (P<0.001) in the Ruxo-ECP cohort, and the cumulative incidence of chronic GvHD was significantly higher after Ruxo versus Ruxo-ECP at 49% (95% CI: 33-69%) versus 24% (95% CI: 15-38%) (P=0.01). Reconstitution of B cells occurred significantly earlier at one and three months in the Ruxo arm. No difference in 1-year non-relapse mortality, relapse, and 2-year overall survival was observed. Despite the limitations of this retrospective single- center study, the data suggest a better long-term control of aGvHD and less chronic GvHD at one year combining ruxolitinib with ECP compared to ruxolitinib alone in SR-aGvHD.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"1536-1544"},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663439","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

Splenectomy: still a life-saving treatment in immune thrombocytopenia. 脾切除术：仍然是挽救免疫性血小板减少症生命的治疗方法。

IF 10.1 1区医学

Haematologica Pub Date : 2025-07-01 DOI: 10.3324/haematol.2025.287512

Francesco Rodeghiero

引用次数: 0

Does allopurinol enhance efficacy of acute lymphoblastic leukemia maintenance therapy? 别嘌呤醇能提高急性淋巴细胞白血病维持治疗的疗效吗？

IF 8.2 1区医学

Haematologica Pub Date : 2025-07-01 Epub Date: 2025-03-20 DOI: 10.3324/haematol.2024.287274

Kjeld Schmiegelow, Linea Natalie Toksvang, Valentino Conter

引用次数: 0

New bispecific antibodies in diffuse large B-cell lymphoma. 弥漫性大b细胞淋巴瘤新的双特异性抗体。