Blood advances最新文献_第2页

NFAT5 counters long-term IFN-I responses in hematopoietic stem cells to preserve reconstitution potential. NFAT5 可对抗造血干细胞中长期的 IFN-I 反应，以保持重建潜力。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2023011306

Laia Traveset, Víctor Cerdán Porqueras, Hector Huerga Encabo, Silvia Avalle, Anna Esteve-Codina, Oscar Fornas, Jose Aramburu, Cristina Lopez-Rodriguez

{"title":"NFAT5 counters long-term IFN-I responses in hematopoietic stem cells to preserve reconstitution potential.","authors":"Laia Traveset, Víctor Cerdán Porqueras, Hector Huerga Encabo, Silvia Avalle, Anna Esteve-Codina, Oscar Fornas, Jose Aramburu, Cristina Lopez-Rodriguez","doi":"10.1182/bloodadvances.2023011306","DOIUrl":"https://doi.org/10.1182/bloodadvances.2023011306","url":null,"abstract":"Hematopoietic stem cells (HSCs) readily recover from acute stress, but persistent stress can reduce their viability and long-term potential. Here we show that the nuclear factor of activated T cells 5 (NFAT5), a transcription modulator of inflammatory responses, protects the HSC pool under stress. NFAT5 restrains HSC differentiation to multipotent progenitors (MPPs) after bone marrow transplantation and bone marrow ablation with ionizing radiation or chemotherapy. Correspondingly, NFAT5-deficient HSCs fail to support long-term reconstitution of hematopoietic progenitors and mature blood cells after serial transplant. Evidence from competitive transplant assays shows that these defects are HSC-intrinsic. NFAT5-deficient HSCs exhibit enhanced expression of type I interferon (IFN-I) response genes after transplant, and suppressing IFN-I-receptor prevents their exacerbated differentiation and cell death after reconstitution and improves long-term regeneration potential. Blockade of IFN-I receptor also prevented the overdifferentiation of NFAT5-deficient HSCs after bone marrow ablation. These findings show that long-term IFN-I responses to different hematopoietic stressors drive HSCs towards more differentiated progenitors, and that NFAT5 has an HSC-intrinsic role limiting IFN-I responses to preserve reconstitution potential. Our identification of cell-intrinsic mechanisms that strengthen the resistance of HSCs to stress could help to devise approaches to protect long-term stemness during the treatment of hematopoietic malignancies.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104485","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

Waldenström Macroglobulinaemia lymphoma patients have impaired platelet and coagulation function. 瓦尔登斯特伦巨球蛋白血症淋巴瘤患者的血小板和凝血功能受损。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024014190

Simone A Brysland, Dipti Talaulikar, Sarah M Hicks, James I Hearn, Sidra Asad Ali, Muhammad Gohar Maqbool, Mridula Mokoonlall, Vijay Bhoopalan, Amandeep Kaur, Yee Lin Thong, Robert K Andrews, James C Whisstock, Philip J Crispin, Elizabeth E Gardiner

{"title":"Waldenström Macroglobulinaemia lymphoma patients have impaired platelet and coagulation function.","authors":"Simone A Brysland, Dipti Talaulikar, Sarah M Hicks, James I Hearn, Sidra Asad Ali, Muhammad Gohar Maqbool, Mridula Mokoonlall, Vijay Bhoopalan, Amandeep Kaur, Yee Lin Thong, Robert K Andrews, James C Whisstock, Philip J Crispin, Elizabeth E Gardiner","doi":"10.1182/bloodadvances.2024014190","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014190","url":null,"abstract":"Clinical features in patients with the B-cell lymphoma, Waldenström Macroglobulinaemia (WM), include cytopenias, IgM-mediated hyperviscosity, fatigue, bleeding and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal haemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not been investigated in WM patients. To evaluate haemostatic dysfunction in samples from WM patients. Whole blood (WB) samples were collected from 14 WM patients not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation ± platelets by FRET assay, WB clotting potential by rotational thromboelastometry (ROTEM), and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by ELISA. Donor platelet spreading, aggregation and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (p=0.0012) while serum TPO levels were increased (p=0.0040). WM plasma displayed slower thrombin generation (p=0.0080) and WM platelets contributed less to endogenous thrombin potential (ETP, p=0.0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (p=0.0002), aggregation (p<0.0001) and ETP (p=0.0081). Alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired haemostasis in vitro. Platelet and coagulation properties are disturbed in well-managed WM patients.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104489","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

Comparison of patients with myeloma receiving zoledronic acid versus denosumab: A nationwide retrospective cohort study. 骨髓瘤患者接受唑来膦酸与地诺单抗治疗的比较：一项全国性回顾性队列研究。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024013600

Ghulam Rehman Mohyuddin, Jenny Guadamuz, Mustafa Ascha, Brian C-H Chiu, Pritesh Patel, Karen Sweiss, Rebecca Rohrer, Douglas W Sborov, Gregory Sampang Calip

引用次数: 0

Thrombomodulin (p.Cys537Stop) is released from cells by an unusual membrane insertion/leakage mechanism. 血栓调节蛋白（p.Cys537Stop）通过一种不寻常的膜插入/泄漏机制从细胞中释放出来。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024013546

Clara Bernard, Andréa Pin, Nathalie Hézard, Vincent Ernest, Céline Falaise, Camille Roze, Stephanie Simoncini, Romaric Lacroix, Pierre-Emmanuel Morange, Franck Peiretti

{"title":"Thrombomodulin (p.Cys537Stop) is released from cells by an unusual membrane insertion/leakage mechanism.","authors":"Clara Bernard, Andréa Pin, Nathalie Hézard, Vincent Ernest, Céline Falaise, Camille Roze, Stephanie Simoncini, Romaric Lacroix, Pierre-Emmanuel Morange, Franck Peiretti","doi":"10.1182/bloodadvances.2024013546","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024013546","url":null,"abstract":"The expression of thrombomodulin variant c.1611C>A (p.Cys537Stop) leads to the synthesis of a protein with no cytoplasmic tail and a transmembrane domain shortened by 3 amino acids (TM536). Little is known about the release mechanism and properties of TM536. Using umbilical vein endothelial cells and peripheral blood-derived endothelial colony-forming cells from a heterozygous carrier of TM536 variant as well as overexpression cell models, we demonstrate that TM536 is released from cells by an unusual mechanism. First, TM536 is inserted into the endoplasmic reticulum membrane, then, due to the low hydrophobicity of its intramembrane domain, it escapes from it and follows the conventional secretory pathway to be released into the extracellular compartment without the involvement of proteolysis. This particular secretion mechanism yields a soluble TM536 that is poorly modified by chondroitin sulfate glycosaminoglycan compared to conventionally secreted soluble forms of thrombomodulin, and therefore has a suboptimal capacity to mediate thrombin-dependent activation of protein C. We also show that TM536 cellular trafficking is altered, with retention in early secretory pathway and increased sensitivity to endoplasmic reticulum-associated degradation. As expected, activation of endoplasmic reticulum-associated degradation increases TM536 degradation and reduces its release. The expression of TM536 at the cell surface is low and its distribution in lipid raft-like membrane microdomains is altered, resulting in low thrombin-dependent PC activation on the cell surface.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104488","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

The duration of iron deficiency burden. 缺铁负担的持续时间。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024014579

Beth Maclean, Mubashshira Tahsin Ahmed, Jayne Lim, Toby Richards

引用次数: 0

Efficacy and Tolerance of Brexucabtagene Autoleucel in Adults with R/R B-ALL : A GRAALL study from the DESCAR-T registry. Brexucabtagene Autoleucel 在成人 R/R B-ALL 患者中的疗效和耐受性：DESCAR-T 登记处的 GRAALL 研究。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024013962

Florence Rabian, David Beauvais, Tony Marchand, Sabine Furst, Anne Huynh, Eolia Brissot, Sébastien Maury, Ludovic Gabellier, Patrice Chevallier, Michael Loschi, Stephanie Nguyen Quoc, Marie Balsat, Ingrid Lafon, Amandine Fayard, Vincent Camus, Celestine Simand, Niels Moya, Cristina Castilla-Llorente, Magalie Joris, Ana Berceanu, Anne Thiebaut-Bertrand, Véronique Lheritier, Eve Gehlkopf, Gabrielle Roth Guepin, Thibaut Tl Leguay, Nicolas Boissel

引用次数: 0

The impact of different doses of oral iron supplementation during pregnancy: a pilot randomized trial. 孕期不同剂量口服铁质补充剂的影响：随机试验。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-29 DOI: 10.1182/bloodadvances.2024013408

Simon J Stanworth, David Churchill, Samaher Sweity, Tom Holmes, Cara Hudson, Rosemary Brown, Stephanie Lax, Joanne Murray, Helen Spiby, Noemi Roy, Andrew Farmer, Chris Gale, Elise Crayton, Fabiana Lorencatto, James Griffiths, Joanne Mullings, Sara Last, Marian Knight

{"title":"The impact of different doses of oral iron supplementation during pregnancy: a pilot randomized trial.","authors":"Simon J Stanworth, David Churchill, Samaher Sweity, Tom Holmes, Cara Hudson, Rosemary Brown, Stephanie Lax, Joanne Murray, Helen Spiby, Noemi Roy, Andrew Farmer, Chris Gale, Elise Crayton, Fabiana Lorencatto, James Griffiths, Joanne Mullings, Sara Last, Marian Knight","doi":"10.1182/bloodadvances.2024013408","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024013408","url":null,"abstract":"The burden of iron-deficiency anemia remains significant during pregnancy. Oral iron is first-line medication, but there is uncertainty about a range of factors including adherence and side-effects of different doses. We conducted a pilot randomized trial to investigate the impact of different doses of oral iron supplementation started early in pregnancy, in non-anemic women, for four main outcomes; recruitment and protocol compliance, adherence, maintenance of maternal hemoglobin and side-effects. Participants at antenatal clinic visits were allocated to one of three trial arms, in a 1:1:1 ratio, as 200mg ferrous sulphate daily, alternate days or three-times per week, with follow-up to delivery. Baseline characteristics of 300 recruited participants were well matched between trial arms. The mean proportion of tablets taken as expected per participant was 82.5% overall (72.3%, 89.6% and 84.5% for the daily, alternate days and three-times a week arm, respectively). There was a lower overall adherence rate in the daily arm (47%) compared with alternate days (62%) and three times per week (61%). Reduction in hemoglobin between randomization and 28 weeks appeared smaller for the daily arm. A range of side-effects were commonly reported at baseline before starting interventions, and by later antenatal visits. Many side effects of iron overlapped with normal pregnancy symptoms. A daily iron dosing schedule might give the best opportunity for delivering an adequate iron load during pregnancy in non-anemic women. Further randomized trials powered on clinical outcomes are needed to establish the clinical effectiveness of oral iron supplementation to prevent iron deficiency anemia. (ISRCTN12911644).","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104487","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

Platelet proteomic profiling reveals potential mediators of immunothrombosis and proteostasis in myeloproliferative neoplasms. 血小板蛋白质组揭示了骨髓增生性肿瘤中免疫血栓形成和蛋白稳态的潜在介质。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-27 DOI: 10.1182/bloodadvances.2023012016

Sarah Kelliher, Sara Gamba, Luisa Weiss, Zhu Shen, Marina Marchetti, Francesca Schieppati, Caitriona Scaife, Stephen Madden, Kathleen Bennett, Anne Fortune, Su Maung, Michael Fay, Fionnuala Ní Áinle, Patricia Maguire, Anna Falanga, Barry Kevane, Anandi Krishnan

引用次数: 0

Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study. 二甲双胍的使用与骨髓增生性肿瘤的风险--一项基于丹麦人群的病例对照研究。

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-27 DOI: 10.1182/bloodadvances.2023012266

Daniel Tuyet Kristensen, Andreas Kiesbye Øvlisen, Lasse Hjort Kyneb Jakobsen, Marianne Tang Severinsen, Louise Hur Hannig, Jørn Starklint, Morten Hagemann Hilsøe, Anders Pommer Vallentin, Mette Brabrand, Hans Carl Hasselbalch, Tarec Christoffer El-Galaly, Anne Stidsholt Roug

{"title":"Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study.","authors":"Daniel Tuyet Kristensen, Andreas Kiesbye Øvlisen, Lasse Hjort Kyneb Jakobsen, Marianne Tang Severinsen, Louise Hur Hannig, Jørn Starklint, Morten Hagemann Hilsøe, Anders Pommer Vallentin, Mette Brabrand, Hans Carl Hasselbalch, Tarec Christoffer El-Galaly, Anne Stidsholt Roug","doi":"10.1182/bloodadvances.2023012266","DOIUrl":"10.1182/bloodadvances.2023012266","url":null,"abstract":"Abstract: Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956234","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

Ending endless follow-up for low-risk CLL? 结束低风险 CLL 的无休止随访？

IF 7.4 1区医学

Blood advances Pub Date : 2024-08-27 DOI: 10.1182/bloodadvances.2024012918

Philip A Thompson

引用次数: 0