Current Opinion in Hematology最新文献

{"title":"The invisible string of coagulation, complement, iron, and inflammation in sickle cell disease.","authors":"Joan D Beckman, Erica M Sparkenbaugh","doi":"10.1097/MOH.0000000000000773","DOIUrl":"10.1097/MOH.0000000000000773","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review provides an update on recent advances in mechanistic studies of thromboinflammatory mechanisms that contribute to the disease pathology in sickle cell disease (SCD). There is a focus on novel pathways, clinical relevance, and translational potential of these findings. We hope to encourage more advances in this area to reduce organ damage in young patients prior to gene therapy, and to serve the aging SCD patient population.</p><p><strong>Recent findings: </strong>Novel insights into the roles of neutrophils, the ADAMTS-13/VWF axis, oxidative stress, and the intrinsic coagulation cascade, as well as relevant clinical trials, are discussed.</p><p><strong>Summary: </strong>Several studies implicate dysregulation of the ADAMTS-13/VWF axis as playing a major role in vaso-occlusive events (VOE) in SCD. Another highlight is reducing iron overload, which has beneficial effects on erythrocyte and neutrophil function that reduce VOE and inflammation. Multiple studies suggest that targeting HO-1/ROS in erythrocytes, platelets, and endothelium can attenuate disease pathology. New insights into coagulation activation identify intrinsic coagulation factor XII as a central regulator of many thromboinflammatory pathologies in SCD. The complement cascade and modulators of neutrophil function and release of neutrophil extracellular traps are also discussed.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"153-158"},"PeriodicalIF":3.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9955769","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}

{"title":"Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report.","authors":"María Teresa Álvarez-Román,&nbsp;Raquel Díaz Merchán,&nbsp;Roberto Carlos Raynero Mellado,&nbsp;Victor Jiménez-Yuste","doi":"10.1097/MOH.0000000000000775","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000775","url":null,"abstract":"<p><strong>Purpose of review: </strong>We present a case of a boy diagnosed in 2007 with severe haemophilia B [factor IX (FIX) concentration < 1%] at age of 9 months. He was initially treated with recombinant FIX concentrates, but changes in regimens were frequent due to spontaneous hemarthros. In 2013, he entered a phase III trial (NCT01662531) and received rIX-FP, IDELVION at 50 IU/kg once a week. Although the boy was safely maintained with this regimen (2015-2017), the number of hemarthros increased after he started to play football. Thus, rIX-FP regimen was modified (40 IU/kg twice/week) to optimize therapy. This modification was efficient on maintaining patient's thought levels (33%), helped during his fully incorporation at school and social life, and significantly improved synovial hypertrophy. In the last year, the boy has not suffered any bleeding episode and his joint situation improved significantly, which allowed reducing doses to weekly recommended doses.</p><p><strong>Recent findings: </strong>FIX replacement therapies with intravenous plasma-derived FIX (pdFIX) or standard half-life recombinant FIX (rFIX) concentrates are hampered by the relatively short terminal elimination half-life (t1/2) of these substances (around 17-34 h), resulting in the need for frequent infusions (e.g. once every 3 or 4 days) to maintain protective FIX levels. In the past years, the first genetically recombinant fusion of rFIX with another protein - a recombinant human albumin - was developed (albutrepenonacog-alfa or rIX-FP; IDELVION) as a strategy to extend the t1/2 of rFIX-FP (around 95 h).</p><p><strong>Summary: </strong>We provide information about the difficult management of a patient with a major bleeding haemorrhagic phenotype, which caused serious limitations in the patient's daily life, impacting his quality of life at his young age, and how the switch to IDELVION allowed the situation to improve considerably.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"175-179"},"PeriodicalIF":3.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012501","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}

{"title":"Tissue factor positive microparticles as a biomarker for increased risk of breast cancer-associated thrombosis: a mini review.","authors":"Regan Bucciol,&nbsp;Maha Othman","doi":"10.1097/MOH.0000000000000774","DOIUrl":"10.1097/MOH.0000000000000774","url":null,"abstract":"<p><strong>Purpose of review: </strong>Cancer-associated thrombosis (CAT), such as venous thromboembolism (VTE), is a frequent complication in cancer patients, resulting in poor prognosis. Breast cancer is not highly thrombogenic but is highly prevalent, resulting in increased VTE cases. Many cancers express tissue factor (TF), a glycoprotein that triggers coagulation. The cancer cells were shown to express and release substantial amounts of TF-positive microparticles (MPTF), associated with a prothrombotic state. This narrative review evaluated the current use of the procoagulant MPTF as a biomarker for thrombosis risk in breast cancer.</p><p><strong>Recent findings: </strong>Tumors of epithelial origin with elevated TF expression have been associated with increased VTE incidence. Thus, studies have affirmed the use of MPTF biomarkers for VTE risk in many cancers. Patients with metastatic breast cancer and CAT were found to exhibit elevated procoagulant microparticles in vitro, due to TF expression. The silencing of TF was associated with decreased microparticle release in breast carcinoma cell lines, associated with decreased coagulation.</p><p><strong>Summary: </strong>CAT is a multifactorial condition, with several various underlying diseases. It is proposed that MPTF may be an effective biomarker for thrombosis risk in breast cancer patients but requires a more systemic evaluation utilizing standardized quantification methods.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"180-185"},"PeriodicalIF":3.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9898320","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}

{"title":"In-vivo functions and regulation of polyphosphate in the vascular system.","authors":"Wen-Chan Huang,&nbsp;Reiner K Mailer,&nbsp;Thomas Renné","doi":"10.1097/MOH.0000000000000771","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000771","url":null,"abstract":"<p><strong>Purpose of review: </strong>Polyphosphate, an inorganic polymer consisting of linearly linked phosphate subunits, is ubiquitously found in living organisms. Functions and regulation of the polymer have been analyzed in plants, bacteria and yeast; however, the roles of polyphosphate in mammals are still emerging.</p><p><strong>Recent findings: </strong>In contrast to synthetic polyphosphate that has been extensively utilized in ex-vivo studies, natural polyphosphate is complexed with bivalent cations (mostly Ca 2+ ) and regardless of chain length, forms microparticles that are retained on the surface of procoagulant platelets, platelet-derived microparticles and cancer extracellular vesicles. On cell surfaces, these Ca 2+ /polyphosphate aggregates initiate the factor XII-driven contact system, triggering proinflammatory and procoagulant reactions through the kallikrein kinin system and intrinsic pathway of coagulation, respectively. Polyphosphate inhibitors interfere with thrombosis while sparing hemostasis, replicating the effect of factor XII neutralizing agents. Furthermore, polyphosphate binds to platelet factor 4, which has implications for autoimmune thrombotic diseases, such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombotic thrombocytopenia (VITT), potentially contributing to their pathogenesis. The metabolism and organ-specific distribution of the polymer remain incompletely defined and is the topic of ongoing research.</p><p><strong>Summary: </strong>Polyphosphate acts as a procoagulant and proinflammatory mediator. Neutralizing polyphosphate provides well tolerated thromboprotection, mimicking the effects of factor XII deficiency.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 5","pages":"159-166"},"PeriodicalIF":3.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269505","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}

{"title":"Deficits in our understanding of natural killer cell development in mouse and human.","authors":"Christopher Schorr, Maya Shraddha Krishnan, Maegan Capitano","doi":"10.1097/MOH.0000000000000765","DOIUrl":"10.1097/MOH.0000000000000765","url":null,"abstract":"<p><strong>Purpose of review: </strong>Natural killer (NK) cells are a type of immune cell that play a crucial role in the defense against cancer and viral infections. The development and maturation of NK cells is a complex process, involving the coordination of various signaling pathways, transcription factors, and epigenetic modifications. In recent years, there has been a growing interest in studying the development of NK cells. In this review, we discuss the field's current understanding of the journey a hematopoietic stem cell takes to become a fully mature NK cell and detail the sequential steps and regulation of conventional NK leukopoiesis in both mice and humans.</p><p><strong>Recent findings: </strong>Recent studies have highlighted the significance of defining NK development stages. Several groups report differing schema to identify NK cell development and new findings demonstrate novel ways to classify NK cells. Further investigation of NK cell biology and development is needed, as multiomic analysis reveals a large diversity in NK cell development pathways.</p><p><strong>Summary: </strong>We provide an overview of current knowledge on the development of NK cells, including the various stages of differentiation, the regulation of development, and the maturation of NK cells in both mice and humans. A deeper understanding of NK cell development has the potential to provide insights into new therapeutic strategies for the treatment of diseases such as cancer and viral infections.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"106-116"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10632585","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}

{"title":"Editorial introduction.","authors":"","doi":"10.1097/MOH.0000000000000768","DOIUrl":"10.1097/MOH.0000000000000768","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"v"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544710","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}

{"title":"Understanding and targeting erythroid progenitor cells for effective cancer therapy.","authors":"Qingfei Wang,&nbsp;Rylee A Poole,&nbsp;Mateusz Opyrchal","doi":"10.1097/MOH.0000000000000762","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000762","url":null,"abstract":"<p><strong>Purpose of review: </strong>It is well described that tumor-directed aberrant myelopoiesis contributes to the generation of various myeloid populations with tumor-promoting properties. A growing number of recent studies have revealed the importance of the previously unappreciated roles of erythroid progenitor cells (EPCs) in the context of cancer, bringing the updated concept that altered erythropoiesis also facilitates tumor growth and progression. Better characterization of EPCs may provide attractive therapeutic opportunities.</p><p><strong>Recent findings: </strong>EPCs represent a heterogeneous population. They exhibit crucial pro-tumor activities by secreting growth factors and modulating the immune response. Cancers induce potent EPC expansion and suppress their differentiation. Recent single-cell transcriptome and lineage tracking analyses have provided novel insight that tumor-induced EPCs are able to be transdifferentiated into immunosuppressive myeloid cells to limit T-cell function and immunotherapy. Therapeutic strategies targeting key factors of EPC-driven immunosuppression, reducing the amount of EPCs, and promoting EPC differentiation and maturation have been extensively investigated.</p><p><strong>Summary: </strong>This review summarizes the current state of knowledge as to the fascinating biology of EPCs, highlights mechanisms by which they exert the tumor promoting activities, as well as the perspectives on future directions and strategies to target these cells for potential therapeutic benefit.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"137-143"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/95/cohem-30-137.PMC10242517.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258474","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}

{"title":"Chediak-Higashi syndrome.","authors":"Mackenzie L Talbert, May Christine V Malicdan, Wendy J Introne","doi":"10.1097/MOH.0000000000000766","DOIUrl":"10.1097/MOH.0000000000000766","url":null,"abstract":"<p><strong>Purpose of review: </strong>Chediak-Higashi syndrome is a rare autosomal recessive disorder characterized by congenital immunodeficiency, bleeding diathesis, pyogenic infection, partial oculocutaneous albinism, and progressive neurodegeneration. Treatment is hematopoietic stem cell transplantation or bone marrow transplantation; however, this does not treat the neurologic aspect of the disease. Mutations in the lysosomal trafficking regulator (LYST) gene were identified to be causative of Chediak-Higashi, but despite many analyses, there is little functional information about the LYST protein. This review serves to provide an update on the clinical manifestations and cellular defects of Chediak-Higashi syndrome.</p><p><strong>Recent findings: </strong>More recent papers expand the neurological spectrum of disease in CHS, to include hereditary spastic paraplegia and parkinsonism. Granule size and distribution in NK cells have been investigated in relation to the location of mutations in LYST. Patients with mutations in the ARM/HEAT domain had markedly enlarged granules, but fewer in number. By contrast, patients with mutations in the BEACH domain had more numerous granules that were normal in size to slightly enlarged, but demonstrated markedly impaired polarization. The role of LYST in autophagosome formation has been highlighted in recent studies; LYST was defined to have a prominent role in autophagosome lysosome reformation for the maintenance of lysosomal homeostasis in neurons, while in retinal pigment epithelium cells, LYST deficiency was shown to lead to phagosome accumulation.</p><p><strong>Summary: </strong>Despite CHS being a rare disease, investigation into LYST provides an understanding of basic vesicular fusion and fission. Understanding of these mechanisms may provide further insight into the function of LYST.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"144-151"},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266575","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}

{"title":"The impact of prenatal inflammation on hematopoietic development.","authors":"Nicole A Tseng,&nbsp;Anna E Beaudin","doi":"10.1097/MOH.0000000000000770","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000770","url":null,"abstract":"<p><strong>Purpose of review: </strong>Inflammation is now recognized as a major regulator of hematopoietic stem cell (HSC) function. Adult hematopoietic stem cells can adaptively modulate hematopoietic output in direct response to acute infection and inflammation. Conversely, prolonged exposure to inflammation can drive impaired HSC function, clonal expansion, and malignant transformation. As compared with adult hematopoiesis, the effects of prenatal inflammation on developing hematopoietic stem cells are understudied.</p><p><strong>Recent findings: </strong>Inflammatory cues directly activate adult HSCs in the bone marrow, but the response of fetal HSCs to maternal inflammation is underexplored. Recent evidence demonstrates that maternal inflammation can be detected by fetal hematopoietic stem and progenitor cells (HSPCs) within the fetal liver and that the same inflammatory cues evoke fundamentally distinct responses during development. The responses of developing stem and progenitor cells and the specialized immune cells they produce have important implications for postnatal hematopoietic output and immune function.</p><p><strong>Summary: </strong>We discuss recent insights into the response of fetal hematopoiesis to prenatal inflammation and examine how recent discoveries regarding the contribution of fetal hematopoiesis to the adult hematopoietic system will influence future studies.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"130-136"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725685","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}

{"title":"Regulation of granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization by the sympathetic nervous system.","authors":"Tomohide Suzuki,&nbsp;Shinichi Ishii,&nbsp;Yoshio Katayama","doi":"10.1097/MOH.0000000000000764","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000764","url":null,"abstract":"<p><strong>Purpose of review: </strong>Granulocyte colony-stimulating factor (G-CSF) is now a standard agent to mobilize hematopoietic stem cells (HSCs) from the bone marrow to circulation. This review introduced mechanistic insights from the aspect of the sympathetic nervous system (SNS).</p><p><strong>Recent findings: </strong>Mobilization efficiency is determined by the balance between promotion and suppression pathways critically regulated by the SNS. G-CSF-induced high catecholaminergic tone promotes mobilization by (1) the strong suppression of osteolineage cells as a hematopoietic microenvironment and (2) fibroblast growth factor 23 production from erythroblasts, which inhibits CXCR4 function in HSCs. Simultaneously, SNS signals inhibit mobilization by (1) prostaglandin E2 production from mature neutrophils to induce osteopontin in osteoblasts to anchor HSCs and (2) angiopoietin-like protein 4 production from immature neutrophils via peroxisome proliferator-activated receptor δ to inhibit BM vascular permeability.</p><p><strong>Summary: </strong>We now know not only the regulatory mechanisms of G-CSF-induced mobilization but also the leads about unfavorable clinical phenomena, such as low-grade fever, bone pain, and poor mobilizers. Recent understanding of the mechanism will assist clinicians in the treatment for mobilization and researchers in the studies of the hidden potential of BM.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"124-129"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10258475","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}