Clonal hematopoiesis driven by DNMT3A and TET2 mutations: role in monocyte and macrophage biology and atherosclerotic cardiovascular disease
Purpose of review
Clonal hematopoiesis of indeterminate potential (CHIP), defined by the presence of somatic mutations in hematopoietic cells, is associated with advanced age and increased mortality due to cardiovascular disease. Gene mutations in DNMT3A and TET2 are the most frequently identified variants among patients with CHIP and provide selective advantage that spurs clonal expansion and myeloid skewing. Although DNMT3A and TET2 appear to have opposing enzymatic influence on DNA methylation, mounting data has characterized convergent inflammatory pathways, providing insights to how CHIP may mediate atheroscleroti...
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: MYELOID BIOLOGY: Edited by Rafael Bejar Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - December 7, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Mechanisms of immunothrombosis in COVID-19
Purpose of review
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2. Over the past year, COVID-19 has posed a significant threat to global health. Although the infection is associated with mild symptoms in many patients, a significant proportion of patients develop a prothrombotic state due to a combination of alterations in coagulation and immune cell function. The purpose of this review is to discuss the pathophysiological characteristics of COVID-19 that contribute to the immunothrombosis.
Recent findings
Endotheliopathy during COVID-19 resu...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Novel concepts in red blood cell clearance
Purpose of review
Red blood cell (RBC) clearance has been studied for decades in many different pathologies, which has revealed different routes of RBC degradation, depending on the situation. This review summarizes the latest mechanistic insights on RBC clearance in different contexts; during homeostatic removal, immune-mediated destruction, and systemic inflammation.
Recent findings
Besides the recognition of a variety of potential ‘eat me’ signals on RBCs, recent evidence suggests that normal RBC degradation is driven by the increase of the adhesive properties of RBCs, mediating the retention in the splee...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Circulating platelet count and glycans
Purpose of the review
This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet removal with platelet production in the bone marrow in health and disease.
Recent findings
This review is focused on the role of carbohydrates, specifically sialic acid moieties, as a central mediator of platelet clearance. We discuss recently identified novel mechanisms of carbohydrate-mediated platelet removal and carbohydrate-binding receptors that mediate platelet removal.
Summary
The platelet production rate by mega...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Recent lessons learned for ex-vivo platelet production
Purpose of review
Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life. Generating sufficient platelets in vitro to replace a unit of collected blood remains a challenge. Here, we examine the latest advances in the regulation of megakaryocyte maturation and expansion along with platelet formation and survival. We also discuss alternative therapies investigated to induce platelet production.
Recent findings
Recent studies examined candidate niche cells in the bone marrow microenvironment for promotin...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Hormetic endoplasmic reticulum stress in hematopoietic stem cells
Purpose of review
Hematopoietic stem cells (HSCs) possess the ability to regenerate over a lifetime in the face of extreme cellular proliferation and environmental stress. Yet, mechanisms that control the regenerative properties of HSCs remain elusive. ER stress has emerged as an important signaling event that supports HSC self-renewal and multipotency. The purpose of this review is to summarize the pathways implicating ER stress as cytoprotective in HSCs.
Recent findings
Recent studies have shown multiple signaling cascades of the unfolded protein response (UPR) are persistently activated in healthy HSCs, sugge...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina Yazdanbakhsh Source Type: research
Emerging therapeutic and preventive approaches to transplant-associated thrombotic microangiopathy
Purpose of review
Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication that can occur in both allogeneic and autologous haematopoietic cellular therapy (HCT) recipients and is associated with significant morbidity and mortality. Although TA-TMA is a complex disease, there is emerging evidence that complement activation and endothelial dysfunction play a key role in the pathophysiology of the disease. The use of eculizumab has improved survival in patients with high risk and severe disease, but mortality rates in treated patients still exceed 30%, highlighting the need for novel approaches.
Rec...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
The role of biomarkers in risk stratification, treatment and outcome in acute GVHD
Purpose of review
Graft-versus-host disease (GVHD) following hematopoietic cell transplant (HCT) has a significant impact on morbidity and mortality among recipients. Predicting the long-term outcomes at the time of diagnosis of GVHD or even after response to up-front therapy can be challenging and only has modest accuracy. With biomarkers available to help guide decision-making, the landscape of GVHD is evolving.
Recent findings
Several acute GVHD biomarkers have been identified, with some better able to categorize patients based on their GVHD severity and potential for refractory disease than standard clinical...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
Clinical experience of coronavirus disease 2019 in hematopoietic cell transplant and chimeric antigen receptor T-cell recipients
Purpose of review
To discuss the clinical experience of coronavirus disease 2019 (COVID-19) in hematopoietic cell transplant and chimeric antigen receptor T-cell therapy recipients over the past year and to identify key knowledge gaps for future research.
Recent findings
Immunocompromised individuals and those with chronic health conditions are especially susceptible to infections, which have had a disproportionate impact on health outcomes during the COVID-19 pandemic. Several studies have evaluated the clinical characteristics and outcomes of transplant and cellular therapy (TCT) recipients who developed COVID...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
The new world: hematopoietic stem cell transplant during a pandemic
This article reviews the adjustments to recipient and donor care that occurred in response to this unprecedented event.
Recent findings
Transplant centers modified algorithms, patient flow, education, and how we provided care. Our donor center partners reworked how donors were evaluated and products delivered to the transplant center. Our professional societies provided guidelines for patient and donor care and rapidly modified these based upon the never-ending stream of new data learned about SARS-CoV-2. Our research organizations provided rapid analyses to ensure the care modifications necessitated did not have a ...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
Detecting and preventing post-hematopoietic cell transplant relapse in AML
Purpose of review
Relapsed disease is the primary cause of mortality for acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (HCT). This review outlines the most recent advances in the detection and prevention of AML relapse following allogeneic HCT.
Recent findings
Conventional methods for predicting post-HCT relapse rely on the molecular and cytogenetics features present at diagnosis. These methods are slow to reflect a growing understanding of the molecular heterogeneity of AML and impact of new therapies on post-HCT outcomes. The use of measurable residual disease (MRD) ...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia
Purpose of review
To discuss the curative potential for chimeric antigen receptor T-cell (CAR-T) therapy, with or without consolidative hematopoietic stem cell transplantation (HCT) in the treatment of children and young adults with B lineage acute lymphoblastic leukemia (B-ALL).
Recent findings
CAR-T targeting CD19 can induce durable remissions and prolong life in patients with relapsed/refractory B-ALL. Whether HCT is needed to consolidate remission and cure relapse/refractory B-ALL following a CD19 CAR-T induced remission remains controversial. Preliminary evidence suggests that consolidative HCT following CA...
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Christine Duncan Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 4, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Still a burning question: the interplay between inflammation and fibrosis in myeloproliferative neoplasms
Purpose of review
Bone marrow fibrosis is the progressive replacement of blood-forming cells by reticulin fibres, caused by the acquisition of somatic mutations in hematopoietic stem cells. The molecular and cellular mechanisms that drive the progression of bone marrow fibrosis remain unknown, yet chronic inflammation appears to be a conserved feature in most patients suffering from myeloproliferative neoplasms.
Recent findings
Here, we review recent literature pertaining to the role of inflammation in driving bone marrow fibrosis, and its effect on the various hematopoietic and nonhematopoietic cell populations...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: CLONAL HEMATOPOIESIS (CHIP) AND MYELODYSPLASIA (MDS): Edited by Borhane Guezguez Source Type: research
