Haematologica最新文献_第8页

Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286537

Hetty E Carraway, Joy Nakitandwe, Alexandru Cacovean, Yan Ma, Brian Munneke, Ganesh Waghmare, Clarissa Mandap, Uzma Ahmed, Nicole Kowalczyk, Thomas Butler, Stephan W Morris

引用次数: 0

Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286010

Sara El Hoss, Panicos Shangaris, John Brewin, Maria Eleni Psychogyiou, Cecilia Ng, Lauren Pedler, Helen Rooks, Érica M F Gotardo, Lucas F S Gushiken, Pâmela L Brito, Kypros H Nicolaides, Nicola Conran, David C Rees, John Strouboulis

{"title":"Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.","authors":"Sara El Hoss, Panicos Shangaris, John Brewin, Maria Eleni Psychogyiou, Cecilia Ng, Lauren Pedler, Helen Rooks, Érica M F Gotardo, Lucas F S Gushiken, Pâmela L Brito, Kypros H Nicolaides, Nicola Conran, David C Rees, John Strouboulis","doi":"10.3324/haematol.2024.286010","DOIUrl":"https://doi.org/10.3324/haematol.2024.286010","url":null,"abstract":"Ineffective erythropoiesis (IE) is defined as the abnormal differentiation and excessive destruction of erythroblasts in the marrow, accompanied by an expanded progenitor compartment and relative reduction in the production of reticulocytes. It is a defining feature of many types of anemia, including beta-thalassemia. GATA1 is an essential transcription factor for erythroid differentiation, known to be implicated in hematological conditions presenting with IE, including beta-thalassemia and congenital dyserythropoietic anemia. However, little is known about the role of GATA1 in the erythropoietic defects recently described in sickle cell anemia (SCA). In the present study, we performed a detailed characterization of the role of GATA1 and ineffective erythropoiesis in SCA using both invitro and in-vivo assay systems. We demonstrate a significant decrease in GATA1 protein levels during SCA erythropoiesis and a concomitant increase in oxidative stress. Furthermore, we found that an increase in the activity of the inflammatory caspase, caspase 1, was driving the decrease in GATA1 levels during SCA erythropoiesis and that, upon inhibition of caspase 1 activity, SCA erythropoiesis was rescued and GATA1 levels partially restored. Our study further elucidates the defect in erythropoiesis in SCA, and may therefore help in the development of novel approaches to normalise the bone marrow niche prior to stem cell transplantation, or facilitate the production of healthy stem cells for gene therapy.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780192","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

Does size matter? Center-specific characteristics and survival after allogeneic hematopoietic cell transplantation for acute myeloid leukemia: an analysis of the German Registry for Stem Cell Transplantation and Cell Therapy.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286385

Wolfgang Bethge, Sarah Flossdorf, Franziska Hanke, Christoph Schmid, Mark Ringhoffer, Stefan Klein, Bernd Hertenstein, Johannes Schetelig, Matthias Stelljes, Thomas Schroeder, Igor Wolfgang Blau, Francis Ayuk, Matthias Eder, Robert Zeiser, Katharina Fleischhauer, Nicolaus Kröger, Peter Dreger

{"title":"Does size matter? Center-specific characteristics and survival after allogeneic hematopoietic cell transplantation for acute myeloid leukemia: an analysis of the German Registry for Stem Cell Transplantation and Cell Therapy.","authors":"Wolfgang Bethge, Sarah Flossdorf, Franziska Hanke, Christoph Schmid, Mark Ringhoffer, Stefan Klein, Bernd Hertenstein, Johannes Schetelig, Matthias Stelljes, Thomas Schroeder, Igor Wolfgang Blau, Francis Ayuk, Matthias Eder, Robert Zeiser, Katharina Fleischhauer, Nicolaus Kröger, Peter Dreger","doi":"10.3324/haematol.2024.286385","DOIUrl":"https://doi.org/10.3324/haematol.2024.286385","url":null,"abstract":"We investigated the effect of center-specific variables on overall survival (OS) after allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML). Eligible were adult patients reported to DRST registry receiving first alloHCT for AML from a related or matched (>= 9/10 HLA-match) unrelated donor 2015-2021. Primary endpoint was OS at 12 months from alloHCT. Univariable and multivariable analyses after best subset selection was performed. Of 5328 patients, 83% received alloHCT in a high-volume center (≥40 alloHCT/year); 90% in a university hospital; 90% in a center performing alloHCT for ≥10 years; and 73% in a Joint Accreditation Committee IHCT-Europe and EBMT (JACIE) accredited center. 52% of the patients were in CR1, and ELN risk was adverse in 37% and intermediate in 42%. On multivariable analysis, center-specific factors predicting adverse 12-month OS were program duration.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780188","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

Intestinal perforation following allogeneic stem cell transplantation caused by Epstein-Barr virus-positive mucocutaneous ulcer.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286488

Klaus Hirschbühl, Tina Schaller, Bruno Märkl, Adriana Amerein, Michael Gebhard, Georg Braun, Susanne Wasserberg, Elisa Sala, Martin Trepel, Christoph Schmid

引用次数: 0

Bone-independent extramedullary disease is associated with inferior overall survival in multiple myeloma patients: a single center, real-world experience.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286409

Ke Xu, Charles Agbuduwe, Nickolaos Kanellias, William Wilson, Annabel McMillan, Xenofon Papanikolaou, Lydia Lee, Rakesh Popat, Jonathan Sive, Neil Rabin, Kwee Yong, Agapi Parcharidou, Charalampia Kyriakou

引用次数: 0

Air pollution, residential greenspace, and the risk of incident immune thrombocytopenic purpura: a prospective cohort study of 356,482 participants.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.286328

Peiyang Luo, Feifan Wang, Jiacheng Ying, Ke Liu, Baojie Hua, Shuhui Chen, Jiayu Li, Xiaohui Sun, Ding Ye, Baodong Ye, Jinyi Tong, Keding Shao, Yingying Mao

{"title":"Air pollution, residential greenspace, and the risk of incident immune thrombocytopenic purpura: a prospective cohort study of 356,482 participants.","authors":"Peiyang Luo, Feifan Wang, Jiacheng Ying, Ke Liu, Baojie Hua, Shuhui Chen, Jiayu Li, Xiaohui Sun, Ding Ye, Baodong Ye, Jinyi Tong, Keding Shao, Yingying Mao","doi":"10.3324/haematol.2024.286328","DOIUrl":"https://doi.org/10.3324/haematol.2024.286328","url":null,"abstract":"This study investigated the associations of air pollution and residential greenspace with immune thrombocytopenic purpura (ITP) risk, along with their combined effects, in a cohort of 356,482 UK Biobank participants free of ITP at baseline. Ambient PM2.5, PMcoarse, PM10, NO2, and NOx exposures were estimated by land-use regression models and residential greenspace was calculated using land use data, defined as the percentage of outdoor greenspace surrounding each participant's home location. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using Cox proportional hazard models, and non-linear relationships were assessed using restricted cubic spline (RCS) curves. A total of 500 incident ITP cases were diagnosed during a median follow-up of 13.54 years. Long-term exposure to high ambient concentrations of PM2.5 (HR = 1.15, 95% CI: 1.04-1.28, P = 0.007), NO2 (HR = 1.23, 95% CI: 1.10-1.37, P = 1.83×10-4), and NOx (HR = 1.12, 95% CI: 1.03-1.21, P = 0.011), as well as low residential greenspace (HR = 0.77, 95% CI: 0.67-0.87, P = 7.96×10-5), were associated with an increased risk of ITP. RCS curve revealed a non-linear relationship of PM10 and NOx with ITP risk (P for non-linearity: 0.003 for PM10 and 0.030 for NOx). Participants with high air pollution and low residential greenspace had the highest risk of ITP, though no evidence of mediation or interaction effects were observed. In conclusion, long-term exposure to ambient PM2.5, PM10, NO2 and NOx may increase ITP risk, whereas residential greenspace may decrease this risk.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780174","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

Evolution of myeloproliferative neoplasms from normal blood stem cells.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2023.283951

Sahand Hormoz, Vijay G Sankaran, Ann Mullally

{"title":"Evolution of myeloproliferative neoplasms from normal blood stem cells.","authors":"Sahand Hormoz, Vijay G Sankaran, Ann Mullally","doi":"10.3324/haematol.2023.283951","DOIUrl":"https://doi.org/10.3324/haematol.2023.283951","url":null,"abstract":"Over the course of the last decade, genomic studies in the context of normal human hematopoiesis have provided new insights into the early pathogenesis of myeloproliferative neoplasms (MPN). A preclinical phase of MPN, termed clonal hematopoiesis (CH) was identified and subsequent lineage tracing studies revealed a multi-decade long time interval from acquisition of an MPN phenotypic driver mutation in a hematopoietic stem cell (HSC) to the development of overt MPN. Multiple germline variants associated with MPN risk have been identified through genome-wide association studies (GWAS) and in some cases functional interrogation of the impact of the variant has uncovered new insights into HSC biology and MPN development. Increasingly sophisticated methods to study clonal contributions to human hematopoiesis and measure HSC fitness have helped discern the biology underlying the tremendous clinical heterogeneity observed in MPN. Despite these advances, significant knowledge gaps remain particularly with respect to germline genetic contributors to both MPN pathogenesis and phenotypic diversity, as well as limitations in the ability to prospectively quantify rates of clonal expansion in individual MPN patients. Ultimately, we envisage a personalized approach to MPN care in the future, where an individualized genetic assessment can predict MPN trajectory and this information will be used to inform and guide therapy. MPN is particularly amenable to precision medicine strategies and our increased understanding of the evolution of MPN from normal blood stem cells provides a unique opportunity for early therapeutic intervention approaches and potentially MPN prevention strategies.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780189","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

Depletion of the RNA binding protein QKI and circular RNA dysregulation in T-cell acute lymphoblastic leukemia.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.285971

Alessia Buratin, Bruno Palhais, Enrico Gaffo, Juliette Roels, Julie Morscio, Jolien Van Laere, Silvia Orsi, Geertruij Te Kronnie, Pieter Van Vlierberghe, Panagiotis Ntziachristos, Stefania Bortoluzzi

引用次数: 0

Treatment of high risk myelodysplastic syndrome.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2023.284946

Nicolaus Kröger

{"title":"Treatment of high risk myelodysplastic syndrome.","authors":"Nicolaus Kröger","doi":"10.3324/haematol.2023.284946","DOIUrl":"https://doi.org/10.3324/haematol.2023.284946","url":null,"abstract":"The myelodysplastic syndrome (MDS) is considered to be a heterogeneous myeloid malignancy with a common origin in the hematopoietic stem cell compartment, generally divided into lower and higher risk. While treatment goal for lower risk MDS (LR-MDS) is to decrease transfusion burden and transformation into acute leukemia major aim for high risk MDS is to prolong survival and ultimately cure. While novel agents such as luspatercept or imetelstat have recently been approved as new treatment options for LR-MDS, hypomethylating agents (HMA) remain currently the only approved non-transplant option for HR-MDS and is the standard of care for non-transplant-eligible patients. Combinations with other drugs as first-line treatment has to date not proven more efficacious than monotherapy in HR-MDS, and outcome after HMA failure is poor. The only potential cure and standard of care for eligible patients is allogeneic stem cell transplantation (HSCT) and even if the number of transplanted - especially older - MDS patients increased over time due to a better management and donor availability the majority of MDS patients will not be eligible for this curative approach. Current challenges encompass to decrease the relapse risk, the main cause of HSCT failure. This review will summarize current knowledge of options of transplant- and non-transplant treatment approaches for these patients and demonstrate the unmet clinical need for more effective therapies.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780193","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

Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed / refractory multiple myeloma.

IF 8.2 1区医学

Haematologica Pub Date : 2024-12-05 DOI: 10.3324/haematol.2024.285587

Ryan T Bishop, Tao Li, Praneeth Sudalagunta, Mostafa Nasr, Karl J Nyman, Raghunandan R Alugubelli, Mark Meads, Jeremy Frieling, Niveditha Nerlakanti, Marilena Tauro, Bin Fang, Steven Grant, John Koomen, Ariosto S Silva, Kenneth H Shain, Conor C Lynch

{"title":"Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed / refractory multiple myeloma.","authors":"Ryan T Bishop, Tao Li, Praneeth Sudalagunta, Mostafa Nasr, Karl J Nyman, Raghunandan R Alugubelli, Mark Meads, Jeremy Frieling, Niveditha Nerlakanti, Marilena Tauro, Bin Fang, Steven Grant, John Koomen, Ariosto S Silva, Kenneth H Shain, Conor C Lynch","doi":"10.3324/haematol.2024.285587","DOIUrl":"https://doi.org/10.3324/haematol.2024.285587","url":null,"abstract":"Multiple myeloma (MM) patients are often refractory to targeted therapies including proteasome inhibitors (PIs). Here, analysis of RNA sequencing data derived from 672 patients with newly diagnosed or relapsed/refractory disease identified the acid ceramidase, ASAH1, as a key regulator of PI resistance. Genetic or pharmacological blockade of ASAH1 remarkably restored PI sensitivity and protected mice from resistant MM progression in vivo. Mechanistically, ASAH1 depletion of ceramide promoted SET inhibition of PP2A phosphatase activity thus facilitating the increased expression and activity of the pro-survival proteins, MCL-1, and BCL-2. We corroborated these findings in human MM datasets, and in ex vivo patient MM cells. These preclinical studies suggest that ASAH1 may be a potential therapeutic target for the treatment of relapsed/refractory MM (RRMM).","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780171","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