Current Opinion in Hematology最新文献_第8页

Understanding and targeting erythroid progenitor cells for effective cancer therapy. 了解和靶向红系祖细胞用于有效的癌症治疗。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-07-01 DOI: 10.1097/MOH.0000000000000762

Qingfei Wang, Rylee A Poole, Mateusz Opyrchal

{"title":"Understanding and targeting erythroid progenitor cells for effective cancer therapy.","authors":"Qingfei Wang, Rylee A Poole, Mateusz Opyrchal","doi":"10.1097/MOH.0000000000000762","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000762","url":null,"abstract":"Purpose of review: 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.Recent findings: 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.Summary: 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.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"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}

引用次数: 1

Chediak-Higashi syndrome. 切迪克-希加希综合征

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2023-07-01 Epub Date: 2023-04-25 DOI: 10.1097/MOH.0000000000000766

Mackenzie L Talbert, May Christine V Malicdan, Wendy J Introne

{"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":"Purpose of review: 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.Recent findings: 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.Summary: 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.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"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}

引用次数: 0

Regulation of granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization by the sympathetic nervous system. 交感神经系统对粒细胞集落刺激因子诱导的造血干细胞动员的调控。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-07-01 DOI: 10.1097/MOH.0000000000000764

Tomohide Suzuki, Shinichi Ishii, Yoshio Katayama

{"title":"Regulation of granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization by the sympathetic nervous system.","authors":"Tomohide Suzuki, Shinichi Ishii, Yoshio Katayama","doi":"10.1097/MOH.0000000000000764","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000764","url":null,"abstract":"Purpose of review: 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).Recent findings: 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.Summary: 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.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"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}

引用次数: 0

Crosstalk between terminal erythropoiesis and granulopoiesis within their common niche: the erythromyeloblastic island. 红细胞生成末期和粒细胞生成末期在其共同的生态位（红细胞母细胞岛）中相互交织。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2023-07-01 Epub Date: 2023-04-25 DOI: 10.1097/MOH.0000000000000767

Laurel Romano, Katie G Seu, Lionel Blanc, Theodosia A Kalfa

{"title":"Crosstalk between terminal erythropoiesis and granulopoiesis within their common niche: the erythromyeloblastic island.","authors":"Laurel Romano, Katie G Seu, Lionel Blanc, Theodosia A Kalfa","doi":"10.1097/MOH.0000000000000767","DOIUrl":"10.1097/MOH.0000000000000767","url":null,"abstract":"Purpose of review: The identity of the erythroblastic island (EBI) macrophage (Mϕ) has been under investigation for decades since it was recognized as the first hematopoietic niche 'nursing' terminal erythropoiesis. This review will focus on the current insights to the characteristics and the role of the EBI Mϕ balancing terminal erythropoiesis and granulopoiesis.Recent findings: While the EBI has long been known as the niche for erythroid precursors, significant advancements in biology research technologies, including optimization of EBI enrichment protocols, single-cell ribonucleic acid sequencing, and imaging flow cytometry, have recently revealed that granulocytic precursors co-exist in this niche, termed erythromyeloblastic island (EMBI). More importantly, the balance noted at baseline between terminal granulopoiesis and erythropoiesis within EBIs/EMBIs is altered with diseases affecting hematopoiesis, such as stress erythropoiesis and inflammatory conditions causing anemia of inflammation. The role of the EMBI niche has yet to be fully investigated mechanistically, however, a notable degree of transcriptional and cell surface marker heterogeneity has been identified for the EMBI Mϕ, implicating its plasticity and diverse function.Summary: Terminal erythropoiesis and granulopoiesis are regulated within the EMBI. Investigations of their balance within this niche in health and disease may reveal new targets for treatment of diseases of terminal hematopoiesis.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266573","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

Interferon regulatory factor-8-dependent innate immune alarm senses GATA2 deficiency to alter hematopoietic differentiation and function. 干扰素调节因子-8 依赖性先天免疫警报感知 GATA2 缺乏，从而改变造血分化和功能。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2023-07-01 Epub Date: 2023-04-27 DOI: 10.1097/MOH.0000000000000763

Kirby D Johnson, Mabel M Jung, Vu L Tran, Emery H Bresnick

{"title":"Interferon regulatory factor-8-dependent innate immune alarm senses GATA2 deficiency to alter hematopoietic differentiation and function.","authors":"Kirby D Johnson, Mabel M Jung, Vu L Tran, Emery H Bresnick","doi":"10.1097/MOH.0000000000000763","DOIUrl":"10.1097/MOH.0000000000000763","url":null,"abstract":"Purpose of review: Recent discoveries have provided evidence for mechanistic links between the master regulator of hematopoiesis GATA2 and the key component of interferon and innate immunity signaling pathways, interferon-regulatory factor-8 (IRF8). These links have important implications for the control of myeloid differentiation in physiological and pathological states.Recent findings: GATA2 deficiency resulting from loss of the Gata2 -77 enhancer in progenitors triggers an alarm that instigates the transcriptional induction of innate immune signaling and distorts a myeloid differentiation program. This pathological alteration renders progenitors hyperresponsive to interferon γ, toll-like receptor and interleukin-6 signaling and impaired in granulocyte-macrophage colony-stimulating factor signaling. IRF8 upregulation in -77-/- progenitors promotes monocyte and dendritic cell differentiation while suppressing granulocytic differentiation. As PU.1 promotes transcription of Irf8 and other myeloid and B-lineage genes, GATA2-mediated repression of these genes opposes the PU.1-dependent activating mechanism.Summary: As GATA2 deficiency syndrome is an immunodeficiency disorder often involving myelodysplastic syndromes and acute myeloid leukemia, elucidating how GATA2 commissions and decommissions genome activity and developmental regulatory programs will unveil mechanisms that go awry when GATA2 levels and/or activities are disrupted.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10266574","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

Erythrocyte pyruvate kinase activation in red cell disorders. 红细胞丙酮酸激酶在红细胞紊乱中的激活。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-05-01 DOI: 10.1097/MOH.0000000000000758

Alessandro Matte, Enrica Federti, Lucia De Franceschi

{"title":"Erythrocyte pyruvate kinase activation in red cell disorders.","authors":"Alessandro Matte, Enrica Federti, Lucia De Franceschi","doi":"10.1097/MOH.0000000000000758","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000758","url":null,"abstract":"Purpose of review: In red cells, pyruvate kinase is a key enzyme in the final step of glycolytic degradative process, which generates a constant energy supply via ATP production. This commentary discusses recent findings on pyruvate kinase activators as new therapeutic option in hereditary red cell disorders such as thalassemic syndromes or sickle cell disease (SCD).Recent findings: Mitapivat and etavopivat are two oral pyruvate kinase activators. Studies in a mouse model for β thalassemia have shown beneficial effects of mitapivat on both red cell survival and ineffective erythropoiesis, with an amelioration of iron homeostasis. This was confirmed in a proof-of-concept study in patients with nontransfusion-dependent thalassemias. Both mitapivat and etavopivat have been evaluated in mouse models for SCD, showing an increased 2-3DPG/ATP ratio and a reduction in haemolysis as well as in sickling. These data were confirmed in proof-of-concept clinical studies with both molecules carried in patients with SCD.Summary: Preclinical and clinical evidence indicate that pyruvate kinase activators represent new therapeutic option in hemoglobinopathies or SCD. Other red cell disorders such as hereditary spherocytosis or hereditary anaemias characterized by defective erythropoiesis might represent additional areas to investigate the therapeutic impact of pyruvate kinase activators.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259003","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: 2

Editorial introduction. 编辑介绍。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-05-01 DOI: 10.1097/MOH.0000000000000759

引用次数: 0

Editorial: Current Opinion in Hematology: new editor announcement. 社论：血液学当前观点：新编辑公告。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-05-01 DOI: 10.1097/MOH.0000000000000761

Sarah J Booth

引用次数: 0

Navigating the marrow sea towards erythromyeloblastic islands under normal and inflammatory conditions. 在正常和炎症条件下，在髓海中寻找红细胞母细胞岛。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-05-01 Epub Date: 2023-01-17 DOI: 10.1097/MOH.0000000000000756

Rachel Josselsohn, Betsy J Barnes, Theodosia A Kalfa, Lionel Blanc

{"title":"Navigating the marrow sea towards erythromyeloblastic islands under normal and inflammatory conditions.","authors":"Rachel Josselsohn, Betsy J Barnes, Theodosia A Kalfa, Lionel Blanc","doi":"10.1097/MOH.0000000000000756","DOIUrl":"10.1097/MOH.0000000000000756","url":null,"abstract":"Purpose of review: Terminal erythroid differentiation occurs in specialized niches called erythroblastic islands. Since their discovery in 1958, these niches have been described as a central macrophage surrounded by differentiating erythroblasts. Here, we review the recent advances made in the characterization of these islands and the role they could play in anaemia of inflammation.Recent findings: The utilization of multispectral imaging flow cytometry (flow cytometry with microscopy) has enabled for a more precise characterization of the niche that revealed the presence of maturing granulocytes in close contact with the central macrophage. These erythromyeloblastic islands (EMBIs) can adapt depending on the peripheral needs. Indeed, during inflammation wherein inflammatory cytokines limit erythropoiesis and promote granulopoiesis, EMBIs present altered structures with increased maturing granulocytes and decreased erythroid precursors.Summary: Regulation of the structure and function of the EMBI in the bone marrow emerges as a potential player in the pathophysiology of acute and chronic inflammation and its associated anaemia.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10633092","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

Hidden behind thromboinflammation: revealing the roles of von Willebrand factor in sickle cell disease pathophysiology. 隐藏在血栓炎症背后:揭示血管性血友病因子在镰状细胞病病理生理中的作用。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2023-05-01 Epub Date: 2023-01-12 DOI: 10.1097/MOH.0000000000000755

Eudorah F Vital, Wilbur A Lam

{"title":"Hidden behind thromboinflammation: revealing the roles of von Willebrand factor in sickle cell disease pathophysiology.","authors":"Eudorah F Vital, Wilbur A Lam","doi":"10.1097/MOH.0000000000000755","DOIUrl":"10.1097/MOH.0000000000000755","url":null,"abstract":"Purpose of review: This review provides an update on the pathophysiology of sickle cell disease (SCD) with a particular focus on the dysregulation of the von Willebrand factor (VWF) - ADAMTS13 axis that contributes to its pathogenesis. In discussing recent developments, we hope to encourage new and ongoing discussions surrounding therapeutic targets for SCD.Recent findings: Within the last 5 years, the role of VWF in the pathophysiology of SCD has been further elucidated and is now a target of study in ongoing clinical trials.Summary: The pathophysiology of SCD is multifaceted, as it involves systemwide vascular activation, altered blood rheology, and the activation of immune responses and coagulative pathways. The presence of VWF in excess in SCD, particularly in its largest multimeric form, greatly contributes to its pathogenesis. Understanding the molecular mechanisms that underly the presence of large VWF multimers in SCD will provide further insight into the pathogenesis of SCD and provide specific targets for therapy.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/37/cohem-30-86.PMC10065920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10267001","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: 1