{"title":"The impact of prenatal inflammation on hematopoietic development.","authors":"Nicole A Tseng, 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, Shinichi Ishii, 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}
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"99-105"},"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}
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 4","pages":"117-123"},"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}
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":"<p><strong>Purpose of review: </strong>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).</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 3","pages":"93-98"},"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}
{"title":"Editorial: Current Opinion in Hematology: new editor announcement.","authors":"Sarah J Booth","doi":"10.1097/MOH.0000000000000761","DOIUrl":"10.1097/MOH.0000000000000761","url":null,"abstract":"","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 3","pages":"79"},"PeriodicalIF":3.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9608549","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}
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 3","pages":"80-85"},"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}
{"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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 3","pages":"86-92"},"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}
{"title":"VEXAS: where do we stand 2 years later?","authors":"Pierre Sujobert, Maël Heiblig, Yvan Jamilloux","doi":"10.1097/MOH.0000000000000750","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000750","url":null,"abstract":"<p><strong>Purpose of review: </strong>Two years after the recognition of VEXAS (for Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, we propose an extensive review of the current understanding of VEXAS pathophysiology and therapeutic options.</p><p><strong>Recent findings: </strong>Among the nearly 150 articles published about VEXAS, some have provided determinant insights into VEXAS pathophysiology and treatment. Clinical data from retrospective series support the JAK inhibitor ruxolitinib as the most efficient strategy to control inflammation, and interesting results were also described with azacytidine. Allogeneic stem cell transplantation remains the only curative option, but should be proposed to carefully selected patients.</p><p><strong>Summary: </strong>Although waiting for more robust evidence from prospective clinical trials, therapeutic options emerge from retrospective studies. We propose a set of criteria that should be systematically reported to harmonize the evaluation of therapeutic outcomes. This will allow the collection of high-quality data and facilitate their subsequent meta-analysis with the overall aim of improving the management of VEXAS patients.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"30 2","pages":"64-69"},"PeriodicalIF":3.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10633099","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}