Blood最新文献 - Book学术

How to make transplanted stem cells feel at home.

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024026611

Rafal Machowicz

引用次数: 0

GSDME-mediated pyroptosis contributes to chemotherapy-induced platelet hyperactivity and thrombotic potential. GSDME 介导的热蛋白沉积有助于化疗引起的血小板过度活跃和血栓形成。

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2023023179

Ruyi Xue, Min Li, Ge Zhang, Wei Zhang, Liping Han, Tao Bo, Haoxuan Zhong, Dingjin Yao, Yiran Deng, She Chen, Si Zhang

{"title":"GSDME-mediated pyroptosis contributes to chemotherapy-induced platelet hyperactivity and thrombotic potential.","authors":"Ruyi Xue, Min Li, Ge Zhang, Wei Zhang, Liping Han, Tao Bo, Haoxuan Zhong, Dingjin Yao, Yiran Deng, She Chen, Si Zhang","doi":"10.1182/blood.2023023179","DOIUrl":"10.1182/blood.2023023179","url":null,"abstract":"Abstract: Thrombotic complications due to platelet hyperreactivity are a major cause of death in patients undergoing chemotherapy. However, the underlying mechanisms are not fully understood. Herein, using human platelets and platelets from mice lacking gasdermin E (GSDME), we show that GSDME is functionally expressed in anucleate platelets, and that GSDME-mediated pyroptosis, a newly identified form of cell death in mammalian nucleated cells, contributes to platelet hyperactivity in cisplatin-based chemotherapy. Cisplatin or etoposide activates caspase-3 to cleave GSDME, thereby releasing the N-terminal fragment of GSDME (GSDME-N) toward the platelet plasma membrane, subsequently forming membrane pores and facilitating platelet granule release. This eventually promotes platelet hyperactivity and thrombotic potential. We identified flotillin-2, a scaffold protein, as a GSDME-N interactor that recruits GSDME-N to the platelet membrane. Loss of GSDME protects mice from cisplatin-induced platelet hyperactivity. Our results provide evidence that targeting GSDME-mediated pyroptosis could reduce thrombotic potential in chemotherapy.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2652-2665"},"PeriodicalIF":21.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387920","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

CAR T-cells in autoimmunity: game changer or stepping stone?

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024025413

Dimitrios Mougiakakos, Everett Meyer, Georg Schett

{"title":"CAR T-cells in autoimmunity: game changer or stepping stone?","authors":"Dimitrios Mougiakakos, Everett Meyer, Georg Schett","doi":"10.1182/blood.2024025413","DOIUrl":"https://doi.org/10.1182/blood.2024025413","url":null,"abstract":"The advent of chimeric antigen receptor (CAR) T-cells has revolutionized the treatment landscape for hematologic malignancies, and emerging evidence suggests their potential in autoimmune diseases (AIDs). This article examines the early successes and future implications of B-cell-targeting CAR T-cell therapy in AIDs. Initial applications, particularly in refractory systemic lupus erythematosus (SLE), have demonstrated significant and durable clinical remissions, with accompanying evaluation of the immune system suggesting a so-called \"reset\" of innate inflammation and adaptive autoimmunity. This has generated widespread interest in expanding this therapeutic approach. CAR T-cells offer unique advantages over other treatment modalities, including very deep B-cell depletion and unique therapeutic activity within inflamed tissues and associated lymph structures. However, the field must address key concerns, including long-term toxicity, particularly the risk of secondary malignancies, and future accessibility given the higher prevalence of AIDs compared to malignancies. Technological advances in cell therapy, such as next-generation CAR T-cells, allogeneic off-the-shelf products and alternative cell types such as regulatory CAR T-cells, are being explored in AIDs to improve efficacy and safety. In addition, bispecific antibodies are emerging as potential alternatives or complements to CAR T-cells, potentially offering comparable efficacy without the need for complex logistics, lymphodepletion and the risk of insertional mutagenesis. As the field evolves, cellular therapists will play a critical role in the multidisciplinary teams managing these complex cases. The transformative potential of CAR T-cells in AIDs is undeniable, but careful consideration of safety, efficacy, and implementation is essential as this novel therapeutic approach moves forward.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863345","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

Fishing for 1q gain is now open in amyloidosis.

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024026676

Anaïs Schavgoulidze, Jill Corre

引用次数: 0

Prominent expansion of EBV+ large B cells obscuring follicular helper T-cell lymphoma.

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024026909

Leonard N Yenwongfai, Ivo M B Francischetti

引用次数: 0

Peripheral T-cell lymphoma: are all patients high risk? 外周 T 细胞淋巴瘤：所有患者都是高危人群吗？

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2023020912

Lauren Shea, Neha Mehta-Shah

{"title":"Peripheral T-cell lymphoma: are all patients high risk?","authors":"Lauren Shea, Neha Mehta-Shah","doi":"10.1182/blood.2023020912","DOIUrl":"10.1182/blood.2023020912","url":null,"abstract":"Abstract: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of mature T-cell neoplasms that represent ∼10% of all non-Hodgkin lymphoma. Outcomes for the majority of patients with PTCL are poor, and treatment approaches have been relatively uniform using cyclophosphamide, doxorubicin, vincristine, and prednisone-based therapy. For example, large registry studies consistently demonstrate 5-year overall survival of ∼30% to 40%. However, as our understanding of the biology underpinning the heterogeneity of PTCL improves and as treatments specifically for PTCL are developed, risk stratification has become a more relevant question. Tools including positron emission tomography-computed tomography and minimal residual disease (MRD) monitoring offer the potential for dynamic risk stratification. In this review, we first summarize registry data describing outcomes in the most common subtypes of PTCL: PTCL not otherwise specified, nodal T-follicular helper cell lymphoma including angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma. We describe current clinically based prognostic indices validated for PTCL and highlight emerging tools for prognostication including novel molecular biomarkers, imaging-based metrics, and MRD dynamics.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2604-2612"},"PeriodicalIF":21.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032163","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

DLBCL: who is high risk and how should treatment be optimized? DLBCL：谁是高危人群，应该如何优化治疗？

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2023020779

Anna Dabrowska-Iwanicka, Grzegorz S Nowakowski

引用次数: 0

Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism. 在降低强度移植前对嗜血细胞淋巴组织细胞增多症进行埃马帕鲁单抗治疗可提高嵌合率。

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024025977

Bethany Verkamp, Sonata Jodele, Anthony Sabulski, Rebecca Marsh, Pearce Kieser, Michael B Jordan

{"title":"Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism.","authors":"Bethany Verkamp, Sonata Jodele, Anthony Sabulski, Rebecca Marsh, Pearce Kieser, Michael B Jordan","doi":"10.1182/blood.2024025977","DOIUrl":"10.1182/blood.2024025977","url":null,"abstract":"Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder driven by interferon gamma (IFN-γ). Emapalumab, an anti-IFN-γ antibody, is approved for the treatment of patients with primary HLH. Hematopoietic stem cell transplantation (HSCT) is required for curing HLH. Reduced-intensity conditioning (RIC) HSCT is associated with improved survival but higher incidences of mixed chimerism and secondary graft failure. To understand the potential impact of emapalumab on post-HSCT outcomes, we conducted a retrospective study of pediatric patients with HLH receiving a first RIC-HSCT at our institution between 2014 and 2022 after treatment for HLH, with or without this agent. Mixed chimerism was defined as <95% donor chimerism and severe mixed chimerism as <25% donor chimerism. Intervention-free survival (IFS) included donor lymphocyte infusion, infusion of donor CD34-selected cells, second HSCT, or death within 5 years after HSCT. Fifty patients met the inclusion criteria; 22 received emapalumab within 21 days before the conditioning regimen, and 28 did not. The use of emapalumab was associated with a markedly lower incidence of mixed chimerism (48% vs 77%; P = .03) and severe mixed chimerism (5% vs 38%; P < .01). IFS was significantly higher in patients receiving emapalumab (73% vs 43%; P = .03). Improved IFS was even more striking in infants aged <12 months, a group at the highest risk for mixed chimerism (75% vs 20%; P < .01). Although overall survival was higher with emapalumab, this difference was not significant (82% vs 71%; P = .39). We show that the use of emapalumab for HLH before HSCT mitigates the risk of mixed chimerism and graft failure after RIC-HSCT.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2625-2636"},"PeriodicalIF":21.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071997","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

Platelets on fire during chemotherapy.

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024026314

K Vinod Vijayan

引用次数: 0

Approaching Hypercalcemia in Monoclonal Gammopathy of Undetermined Significance: Insights from the iStopMM study.

IF 21 1区医学

Blood Pub Date : 2024-12-19 DOI: 10.1182/blood.2024025624

Ástrún Helga Jónsdóttir, Helga Ágústa Sigurjónsdóttir, Sigrun Thorsteinsdottir, Thorir Einarsson Long, Ingigerður Sólveig Sverrisdóttir, Elias Eythorsson, Jon Thorir Oskarsson, Runólfur Pálsson, Olafur Skuli Indridason, Bryjnar Vidarsson, Pall T Onundarson, Isleifur Olafsson, Ingunn Þorsteinsdóttir, Bjarni A Agnarsson, Margret Sigurdardottir, Asbjorn Jonsson, Malin L Hultcrantz, Brian G M Durie, Stephen Harding, Carl Ola Landgren, Thorvardur Jon Love, Sigurdur Yngvi Kristinsson, Sæmundur Rögnvaldsson

{"title":"Approaching Hypercalcemia in Monoclonal Gammopathy of Undetermined Significance: Insights from the iStopMM study.","authors":"Ástrún Helga Jónsdóttir, Helga Ágústa Sigurjónsdóttir, Sigrun Thorsteinsdottir, Thorir Einarsson Long, Ingigerður Sólveig Sverrisdóttir, Elias Eythorsson, Jon Thorir Oskarsson, Runólfur Pálsson, Olafur Skuli Indridason, Bryjnar Vidarsson, Pall T Onundarson, Isleifur Olafsson, Ingunn Þorsteinsdóttir, Bjarni A Agnarsson, Margret Sigurdardottir, Asbjorn Jonsson, Malin L Hultcrantz, Brian G M Durie, Stephen Harding, Carl Ola Landgren, Thorvardur Jon Love, Sigurdur Yngvi Kristinsson, Sæmundur Rögnvaldsson","doi":"10.1182/blood.2024025624","DOIUrl":"https://doi.org/10.1182/blood.2024025624","url":null,"abstract":"Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge since it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the iStopMM screening study. Of the 75,422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2,546 with MGUS who were in active follow-up, including regular serum calcium measurements. In total, 191 individuals (7.5%) had hypercalcemia detected at least once, of whom 93 had persistent hypercalcemia (48.7%). MM was found in 3 participants with persistent hypercalcemia (3.2%); all had concurrent bone disease and other end-organ damage. The most common causes of hypercalcemia were primary hyperparathyroidism (56.0%) and malignancies other than MM (16.0%). In this first comprehensive study on hypercalcemia in MGUS, we observed that hypercalcemia rarely indicated MGUS progression and never in the absence of other symptoms of MM. More than half of hypercalcemia cases were transient and the underlying causes were similar to those in the general population. We conclude that hypercalcemia in MGUS should be approached in the same way as in those without MGUS.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863341","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