Current Opinion in Hematology最新文献_第8页

The future of HOXA- expressing leukemias: Menin inhibitor response and resistance. 表达hoxa的白血病的未来:Menin抑制剂的反应和耐药性。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-03-01 Epub Date: 2023-11-23 DOI: 10.1097/MOH.0000000000000796

Daniela V Wenge, Scott A Armstrong

{"title":"The future of HOXA- expressing leukemias: Menin inhibitor response and resistance.","authors":"Daniela V Wenge, Scott A Armstrong","doi":"10.1097/MOH.0000000000000796","DOIUrl":"10.1097/MOH.0000000000000796","url":null,"abstract":"Purpose of review: We provide an update on the successes and ongoing challenges of Menin inhibition as a novel approach for the treatment of patients with acute leukemias that express HOXA cluster genes including leukemias with KMT2A -rearrangements, NPM1 mutations or NUP98 -rearrangements. Initial clinical trials show promising response rates in heavily pretreated patients suggesting these inhibitors may have a significant impact on patient outcome. Furthermore, the development of resistance mutations that decrease drug binding affinity, validates Menin as a therapeutic target in human cancers. Therapeutic strategies aiming at overcoming and preventing resistance, are of high clinical relevance.Recent findings: Several Menin inhibitor chemotypes have entered clinical trials. Acquired point mutations have recently been described as a mechanism of resistance towards Menin inhibitors. However, resistance can develop in absence of these mutations. Combination therapies are currently being investigated in preclinical models and in early phase clinical trials.Summary: Given the remarkable overall response rates, shedding light on treatment options for patients whose leukemias develop resistance to Menin inhibitors is an imminent clinical need. Studying the underlying mechanisms to inform clinical decision making, and to potentially prevent the development of resistance is of outmost importance.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"64-70"},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138447101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Transfusion avoidance in myelodysplastic neoplasms. 骨髓增生异常肿瘤的输血避免。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-03-01 Epub Date: 2023-11-16 DOI: 10.1097/MOH.0000000000000794

Elizabeth A Griffiths

{"title":"Transfusion avoidance in myelodysplastic neoplasms.","authors":"Elizabeth A Griffiths","doi":"10.1097/MOH.0000000000000794","DOIUrl":"10.1097/MOH.0000000000000794","url":null,"abstract":"Purpose of review: Myelodysplastic neoplasms (MDS) are diseases of stem cell aging associated with complications from inadequate hematopoiesis (red cells, neutrophils and platelets) and variable risk for transformation to acute myeloid leukemia. Those with low-risk disease also suffer and die from MDS-related complications. Among the most challenging is development of anemia and transfusion dependence, which impacts quality of life and is associated with reduced survival. Appreciating and measuring the quality-of-life impact, preventing (if possible), treating, and managing the complications from anemia in MDS are of critical importance.Recent findings: Recent developments in basic science highlight the potential deleterious impact of iron overload within the developing red cell niche. Iron overload can compromise red cell maturation from healthy as well as malignant clones and produces an environment favoring expansion of mutant clonal cells, potentially driving disease progression. Observational studies in nontransfusion dependent MDS highlight that iron overload occurs even in the nontransfusion dependent. The newly approved (and established) therapies for management of MDS-related anemia work best when begun before patients become heavily transfusion-dependent.Summary: Iron overload is detrimental to hematopoiesis. Understanding the benefit afforded by transfusion is critical to optimal application and patient reported outcomes can inform this. Recently developed therapies are active and optimized application may improve response.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"40-46"},"PeriodicalIF":3.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Factor XI as a therapeutic target in neuroinflammatory disease. 因子XI作为神经炎症性疾病的治疗靶点。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-09-05 DOI: 10.1097/MOH.0000000000000787

Berk Taskin, Tia C L Kohs, Joseph J Shatzel, Cristina Puy, Owen J T McCarty

{"title":"Factor XI as a therapeutic target in neuroinflammatory disease.","authors":"Berk Taskin, Tia C L Kohs, Joseph J Shatzel, Cristina Puy, Owen J T McCarty","doi":"10.1097/MOH.0000000000000787","DOIUrl":"10.1097/MOH.0000000000000787","url":null,"abstract":"Purpose of review: This review summarizes the pathophysiology and potential therapeutic options for treatment of multiple sclerosis, a common neuronal demyelinating disorder affecting 2.2 million people worldwide. As an autoimmune disorder, multiple sclerosis is associated with neuroinflammation and increased permeability of the blood-brain barrier (BBB), although the cause linking multiple sclerosis with compromised barrier function remains ill-defined. It has been previously shown that coagulation factors, including thrombin and fibrin, exacerbate the inflammatory processes and permeability of the BBB.Recent findings: Increased levels of the coagulation factor (F) XII have been found in patients presenting with relapsing-remitting multiple sclerosis, with a deleterious role for FXII being validated in murine model of multiple sclerosis, experimental autoimmune encephalitis (EAE). Recent work has uncovered a role for the major substrate activated by FXII and thrombin, FXI, in the disorder of EAE. The study found that pharmacological targeting of FXI decreased clinical symptoms, lymphocyte invasion, and white matter destruction in a multiple sclerosis model.Summary: This review emphasizes the role of FXII and FXI in regulating barrier function and the immune response in neuroinflammation. These new findings broaden the potential for therapeutic utility of FXI inhibitors beyond thrombosis to include neuroinflammatory diseases associated with compromised BBB function, including multiple sclerosis.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"32-38"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10308628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Modelling arterial thrombus formation in vitro. 体外模拟动脉血栓形成。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-11-03 DOI: 10.1097/MOH.0000000000000789

Amelia Drysdale, Azziza Zaabalawi, Sarah Jones

{"title":"Modelling arterial thrombus formation in vitro.","authors":"Amelia Drysdale, Azziza Zaabalawi, Sarah Jones","doi":"10.1097/MOH.0000000000000789","DOIUrl":"10.1097/MOH.0000000000000789","url":null,"abstract":"Purpose of review: Models of arterial thrombus formation represent a vital experimental tool to investigate platelet function and test novel antithrombotic drugs. This review highlights some of the recent advances in modelling thrombus formation in vitro and suggests potential future directions.Recent findings: Microfluidic devices and the availability of commercial chips in addition to enhanced accessibility of 3D printing has facilitated a rapid surge in the development of novel in-vitro thrombosis models. These include progression towards more sophisticated, 'vessel on a chip' models which incorporate vascular endothelial cells and smooth muscle cells. Other approaches include the addition of branches to the traditional single channel to yield an occlusive model; and developments in the adhesive coating of microfluidic chambers to better mimic the thrombogenic surface exposed following plaque rupture. Future developments in the drive to create more biologically relevant chambers could see a move towards the use of human placental vessels, perfused ex-vivo. However, further work is required to determine the feasibility and validity of this approach.Summary: Recent advances in thrombus formation models have significantly improved the pathophysiological relevance of in-vitro flow chambers to better reflect the in-vivo environment and provide a more translational platform to test novel antithrombotics.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"16-23"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Platelet mechanosensing as key to understanding platelet function. 血小板力学是理解血小板功能的关键。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-10-16 DOI: 10.1097/MOH.0000000000000788

Ingmar Schoen, Martin Kenny, Smita Patil

{"title":"Platelet mechanosensing as key to understanding platelet function.","authors":"Ingmar Schoen, Martin Kenny, Smita Patil","doi":"10.1097/MOH.0000000000000788","DOIUrl":"10.1097/MOH.0000000000000788","url":null,"abstract":"Purpose of review: This review highlights how the perception of platelet function is evolving based on recent insights into platelet mechanobiology.Recent findings: The mechanosensitive ion channel Piezo1 mediates activation of free-flowing platelets under conditions of flow acceleration through mechanisms independent of adhesion receptors and classical activation pathways. Interference with the initiation of platelet migration or with the phenotypic switch of migrating platelets to a procoagulant state aggravates inflammatory bleeding. Mechanosensing of biochemical and biophysical microenvironmental cues during thrombus formation feed into platelet contractile force generation. Measurements of single platelet contraction and bulk clot retraction show promise to identify individuals at risk for hemorrhage.Summary: New findings unravel novel mechanotransduction pathways and effector functions in platelets, establishing mechanobiology as a pivotal component of platelet function. These insights highlight limitations of existing treatments and offer new potential therapeutic approaches and diagnostic avenues based on mechanobiological principles. Further extensive research is required to distinguish between core hemostatic and pathological mechanisms influenced by platelet mechanosensing.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"24-31"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Editorial introductions. 编辑介绍。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-12-07 DOI: 10.1097/MOH.0000000000000790

引用次数: 0

The many faces of the megakaryocytes and their biological implications. 巨核细胞的多面性及其生物学意义。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-11-01 DOI: 10.1097/MOH.0000000000000793

Karen Guo, Kellie R Machlus, Virginia Camacho

{"title":"The many faces of the megakaryocytes and their biological implications.","authors":"Karen Guo, Kellie R Machlus, Virginia Camacho","doi":"10.1097/MOH.0000000000000793","DOIUrl":"10.1097/MOH.0000000000000793","url":null,"abstract":"Purpose of review: Single-cell RNA sequencing studies have revealed transcriptional heterogeneity within the megakaryocytic lineage and the identified unique subsets. In this review, we discuss the functional and phenotypic plasticity of these subpopulations as well as the impacts on health and disease.Recent findings: Megakaryocytes (MKs) can be transcriptionally categorized into platelet generating, niche supporting, immune, and cycling cells, which are distinguished by their unique gene expression patterns and cellular markers. Additionally, a significant population of these cells has been established to reside in the nonhematopoietic tissues and they display enhanced immune-related characteristics. Combined with the location in which the megakaryocytes exist, these cells can play unique roles dictated by their current environment and biological needs, including responding to changes in pathogen exposure.Summary: Advances in megakaryocyte research has elucidated the existence of multiple subpopulations of MKs that serve different functions. These subpopulations implicate a greater potential for MKs to be regulators of health and suggest new avenues for treatments and therapies in related diseases.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"1-5"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Platelet lifespan and mechanisms for clearance. 血小板寿命和清除机制。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-01-01 Epub Date: 2023-10-30 DOI: 10.1097/MOH.0000000000000792

Olga An, Carsten Deppermann

{"title":"Platelet lifespan and mechanisms for clearance.","authors":"Olga An, Carsten Deppermann","doi":"10.1097/MOH.0000000000000792","DOIUrl":"10.1097/MOH.0000000000000792","url":null,"abstract":"Purpose of review: Activated or aged platelets are removed from circulation under (patho)physiologic conditions, the exact mechanism of platelet clearance under such conditions remains unclear and are currently being investigated. This review focuses on recent findings and controversies regarding platelet clearance and the disruption of platelet life cycle.Recent findings: The platelet life span is determined by glycosylation of platelet surface receptors with sialic acid. Recently, it was shown that platelet activation and granule release leads to desialylation of glycans and accelerated clearance of platelets under pathological conditions. This phenomenon was demonstrated to be a main reason for thrombocytopenia being a complication in several infections and immune disorders.Summary: Although we have recently gained some insight into how aged platelets are cleared from circulation, we are still not seeing the full picture. Further investigations of the platelet clearance pathways under pathophysiologic conditions are needed as well as studies to unravel the connection between platelet clearance and platelet production.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"6-15"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mixed donor chimerism following stem cell transplantation for sickle cell disease. 镰状细胞病干细胞移植后的混合供体嵌合。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-11-01 Epub Date: 2023-09-01 DOI: 10.1097/MOH.0000000000000786

Niketa C Shah, Hemalatha G Rangarajan, Alexander Ngwube, Shalini Shenoy

{"title":"Mixed donor chimerism following stem cell transplantation for sickle cell disease.","authors":"Niketa C Shah, Hemalatha G Rangarajan, Alexander Ngwube, Shalini Shenoy","doi":"10.1097/MOH.0000000000000786","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000786","url":null,"abstract":"Sickle cell disease is a debilitating hemoglobinopathy with high morbidity and mortality. Hematopoietic stem cell transplantation (HCT) is curative, but the presence of mixed donor/recipient chimerism post-HCT raises concerns about disease control long-term. Mixed donor/recipient chimerism is reported in significant numbers even after aggressive HCT conditioning regimens. Post-HCT, adequacy of donor erythropoiesis is crucial for disease control. This review explores the relationship between mixed donor/recipient chimerism and outcomes post-HCT. Serial chimerism analysis in lineage specific manner in erythroid or myeloid cells post-HCT predicts for disease control and HCT success. Adequate and stable donor-derived erythropoiesis is essential for reversing SCD manifestations. Myeloid lineage chimerism mirrors erythropoiesis is commercially available, and a reliable indicator of adequacy. Using this tool, the minimum threshold of donor chimerism is required to prevent SCD-related complications and maintain sickle hemoglobin less than 50% is approximately 20-25% even when a donor has Hb S trait. Curative interventions should, at a minimum, meet this goal long-term. Achieving a balance between successful engraftment while minimizing toxicity is important in patients vulnerable because of age or preexisting morbidity and is the objective of recent clinical trials. As HCT and gene therapies evolve, efficient long-term follow-up that includes durability assessment of mixed donor/recipient chimerism will be crucial.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"187-193"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 immunology of PF4 polyanion interactions. PF4多阴离子相互作用的免疫学。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-11-01 Epub Date: 2023-08-28 DOI: 10.1097/MOH.0000000000000782

Anh T P Ngo, Veronica Bochenek, Kandace Gollomp

{"title":"The immunology of PF4 polyanion interactions.","authors":"Anh T P Ngo, Veronica Bochenek, Kandace Gollomp","doi":"10.1097/MOH.0000000000000782","DOIUrl":"10.1097/MOH.0000000000000782","url":null,"abstract":"Purpose of review: Platelet factor 4 (PF4, CXCL4), the most abundant α-granule platelet-specific chemokine, forms tetramers with an equatorial ring of high positive charge that bind to a wide range of polyanions, after which it changes conformation to expose antigenic epitopes. Antibodies directed against PF4 not only help to clear infection but can also lead to the development of thrombotic disorders such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombocytopenia and thrombosis (VITT). This review will outline the different mechanisms through which PF4 engagement with polyanions combats infection but also contributes to the pathogenesis of inflammatory and thrombotic disease states.Recent findings: Recent work has shown that PF4 binding to microbial polyanions may improve outcomes in infection by enhancing leukocyte-bacterial binding, tethering pathogens to neutrophil extracellular traps (NETs), decreasing the thrombotic potential of NET DNA, and modulating viral infectivity. However, PF4 binding to nucleic acids may enhance their recognition by innate immune receptors, leading to autoinflammation. Lastly, while HIT is induced by platelet activating antibodies that bind to PF4/polyanion complexes, VITT, which occurs in a small subset of patients treated with COVID-19 adenovirus vector vaccines, is characterized by prothrombotic antibodies that bind to PF4 alone.Summary: Investigating the complex interplay of PF4 and polyanions may provide insights relevant to the treatment of infectious disease while also improving our understanding of the pathogenesis of thrombotic disorders driven by anti-PF4/polyanion and anti-PF4 antibodies.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 6","pages":"219-229"},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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