Bone morphogenetic protein and blood vessels: new insights into endothelial cell junction regulation
Purpose of review BMP signaling is an important regulator of vascular development and homeostasis, and perturbations of BMP pathway components are linked to vascular disease. However, until recently BMP's broad requirements in many developmental programs delayed cause-and-effect and mechanistic studies of its vascular role in vivo. This review covers recent findings that illuminate the role of BMP signaling in endothelial cells of blood vessels, and highlights effects of BMP signaling on endothelial cell junctions and vascular barrier function. Recent findings BMP signaling in endothelial cells of blood vessels is con...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

A focus on vascular malformations
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Oxidation and erythropoiesis
Purpose of review Erythropoiesis is a complex multistep process going from committed erythroid progenitors to mature red cells. Although recent advances allow the characterization of some components of erythropoiesis, much still remains to be investigated particularly on stress erythropoiesis. This review summarizes recent progresses made to understand the impact of oxidative stress on normal and pathologic erythropoiesis. Recent findings During erythroid maturation, reactive oxygen species might function as second messenger through either transient oxidation of cysteine residues on signaling targets or modulation of ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Strategies for managing transfusional iron overload: conventional treatments and novel strategies
Purpose of review For individuals who have transfusion-dependent anemia, iron overload is the long-term complication, which results in significant morbidity. Ameliorating this is now the biggest unmet need. This review specifically addresses this issue. Recent findings Over the last decade or so, major advances in the treatment of these individuals, has resulted from novel strategies aimed at reducing transfusion requirement as well as optimizing chelation therapy. This review will summarize these advances and provide insights into some of the therapies in the pipeline. Strategies aimed at reducing transfusion require...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Pain and sickle cell disease
Purpose of review Pain is a major comorbidity of sickle cell disease (SCD). Opioids are the mainstay for pain treatment but remain suboptimal. We discuss mechanism-based treatable targets devoid of opioids to prevent and/or treat SCD pain. Recent findings Understanding the pathogenesis of pain is critical to develop targeted therapies. Nevertheless, acute and chronic pain can have independent and/or overlapping mechanisms. The origin of pain involves neurovascular and neuroimmune interactions from the periphery and/or central nervous system. Immunomodulatory components of acute and/or chronic sickle pain for targeting...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

New insights into the links between hypoxia and iron homeostasis
Purpose of review This review outlines recent discoveries on the crosstalk between oxygen metabolism and iron homeostasis, focusing on the role of HIF-2 (hypoxia inducible factor-2) in the regulation of iron metabolism under physiopathological conditions. Recent findings The importance of the hepcidin/ferroportin axis in the modulation of intestinal HIF-2 to regulate iron absorption has been recently highlighted. Latest advances also reveal a direct titration of the bone morphogenetic proteins by the erythroferrone contributing to liver hepcidin suppression to increase iron availability. Iron is recycled thanks to ery...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Novel tyrosine kinase inhibitors for patients with inadequate response in chronic myeloid leukemia
Purpose of review The purpose of this review is to summarize treatment expectations and response milestones, to conceptualize the approach to defining inadequate response to therapy and critically appraise current available strategies, as well to highlight novel agents under development to address unmet needs in chronic myeloid leukemia (CML) therapy. Recent findings Given excess risk with currently available highly potent ABL1 (Abelson murine leukemia viral oncogene homolog 1) inhibitors, a number of alternate, highly potent compounds have entered the clinic to address select resistance such as the T315I mutation wit...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Novel Approaches for Systemic Mastocytosis
Purpose of review The purpose of this review is to summarize the pathophysiology of systemic mastocytosis, review the most recent clinical trials and drug development in systemic mastocytosis, with a specific focus on the advanced systemic mastocytosis subtypes. Recent findings Systemic mastocytosis is a clonal neoplasm of mast cells that has had a number of successful therapeutic options being developed in the past few years. The first therapeutic agent to be Food and Drug Administration (FDA) approved in decades was midostaurin in 2017 with a 60% response rate % with improvement in both end-organ damage and symptoms...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Posttransplant maintenance therapy for acute leukemias
Purpose of review Allogeneic hematopoietic stem cell transplantation cures a significant proportion of patients with hematological malignancies. Unfortunately, leukemia recurrence is the main cause of transplant failure. Risk factors for relapse include presence of minimal residual disease and a variety of well-recognized leukemia prognostic factors. Posttransplant therapy could decrease the risk of leukemia relapse and is under investigation. In this review, we summarize the current research in maintenance therapy for the prevention of acute leukemia recurrence after allogeneic transplant. Recent findings Epigenetic ...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Progress in the problem of relapsed or refractory acute myeloid leukemia
Purpose of review The majority of patients with acute myeloid leukemia (AML) die from disease recurrence and historically, treatment options in both the relapsed and refractory settings of this disease have been limited. However, new insights into the molecular characterization and biology of relapsed and refractory AML have led to novel therapeutics and improvement in outcomes in these settings. The current understanding of mechanisms of disease resistance and status of treatment options both currently available and under exploration in relapsed and refractory AML are summarized in this review. Recent findings The ra...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

What are the most promising new agents in myelodysplastic syndromes?
Purpose of review Myelodysplastic syndromes (MDS) are a diverse group of clonal disorders of hematopoietic stem or progenitor cells that represent the most common class of acquired bone marrow failure syndromes in adults. Despite significant improvement in the pathologic insight into this group of disorders, therapeutic options remain limited and allogeneic hematopoietic stem-cell transplantation is the only treatment that can induce long-term remission in patients with MDS. The goals of therapy for MDS are based on disease prognostication, with a focus of minimizing transfusion dependence and preserving quality of life ...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective?
Purpose of review Venetoclax with backbone therapies have shown promising efficacy for newly diagnosed, previously untreated, older, unfit acute myeloid leukemia patients. This review discusses this data and potential reasons for the efficacy of these venetoclax-based combinations. Recent findings Venetoclax with hypomethylators and low-dose cytarabine have resulted in high response rates, promising response durations, and significant overall survival in relatively small, uncontrolled studies. There is emerging data that these responses are due to the effective targeting of leukemia stem cells through an alteration of...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Outpatient induction and consolidation care strategies in acute myeloid leukemia
Purpose of review Patients with acute myeloid leukemia (AML) are almost invariably kept in the hospital until resolution of cytopenias following intensive induction chemotherapy. This care approach is costly and may further contribute to the reduced qualify of life of these patients. This has raised interest in moving at least part of this care to the outpatient setting. Reimbursement challenges for inpatient administration of some of the new drugs approved for AML in the last 2 years adds to this interest. Recent findings Retrospective and smaller prospective studies have shown that outpatient management following in...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Which patients with acute myeloid leukemia in CR1 can be spared an allogeneic transplant?
Purpose of review Disease relapse remains the major cause of treatment failure in adults with acute myeloid leukemia (AML) in first complete remission (CR1) treated with intensive chemotherapy alone. Allogeneic stem cell transplantation (allo-SCT) reduces the risk of disease recurrence, and thus the advent of reduced intensity-conditioning regimens coupled with increased donor availability has increased the deliverability of potentially curative transplant therapy in AML. However, allo-SCT remains associated with significant additional morbidity and mortality, and it is therefore important to identify patients whose outc...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Shifting therapeutic paradigms in induction and consolidation for older adults with acute myeloid leukemia
Purpose of review As the age and life expectancy of the general population rise, the number of acute myeloid leukemia (AML) patients suitable for therapy is expected to dramatically increase. The population of older adults with AML, while already comprising the vast majority of AML patients, has not been specifically addressed in terms of unique age-related features, such as existence of comorbidities, frailty, and disease biology. Recent findings Over the past decade, major improvements in the approach to the management of older adults with AML included: incorporation of new comorbidity scores specifically oriented t...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research

Cell biology of activated protein C
Purpose of review The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline t...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: SPECIAL COMMENTARY Source Type: research

Mechanisms of leukemic transformation in congenital neutropenia
Purpose of review The development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia is now the major cause of mortality. Treatment options are limited and there are no effective prevention strategies. This review focuses on mechanisms of leukemic transformation in severe congenital neutropenia (SCN) and Shwachman–Diamond syndrome (SDS), the two most common types of congenital neutropenia. Recent findings AML/MDS that develops in the setting of congenital neutropenia has distinct molecular features. Clonal hematopoiesis because of TP53 mutations is seen in...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics
Purpose of review CXCR2 is key stimulant of immune cell migration and recruitment, especially of neutrophils. Alleviating excessive neutrophil accumulation and infiltration could prevent prolonged tissue damage in inflammatory disorders. This review focuses on recent advances in our understanding of the role of CXCR2 in regulating neutrophil migration and the use of CXCR2 antagonists for therapeutic benefit in inflammatory disorders. Recent findings Recent studies have provided new insights into how CXCR2 signaling regulates hematopoietic cell mobilization and function in both health and disease. We also summarize sev...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

The clinical consequences of neutrophil priming
Purpose of review Neutrophils priming has been long studied in vitro. Recent studies describe it in vivo. In pathophysiological conditions, complex, heterogeneous characteristics of priming are described in the last few years. Recent findings Priming can occur systemically when insults such as sepsis or trauma result in an array of circulating mediators and circulating primed neutrophils seem to exert detrimental effects either directly, or indirectly by interacting with other cells, thereby contributing to the development of organ dysfunction. Local priming of neutrophils augments their ability to clear infection, bu...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor
Purpose of review Glycogen storage disease Ib (GSD Ib) is characterized by hepatomegaly, hypoglycemia, neutropenia, enterocolitis and recurrent bacterial infections. It is attributable to mutations in G6PT1, the gene for the glucose-6-phosphate transporter responsible for transport of glucose into the endoplasmic reticulum. Neutropenia in GSD Ib is now frequently treated with granulocyte colony-stimulating factor (G-CSF). We formed a cooperative group to review outcomes of the long-term treatment of GSD Ib patients treated with G-CSF. Recent findings The study enrolled 103 patients (48 men and 55 women), including 47 ...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Neutropenia in Barth syndrome: characteristics, risks, and management
Purpose of review Barth syndrome (BTHS) is an X-linked disease characterized by defective remodeling of phospholipid side chains in mitochondrial membranes. Major features include neutropenia, dilated cardiomyopathy, motor delay and proximal myopathy, feeding problems, and constitutional growth delay. We conducted this review of neutropenia in BTHS to aid in the diagnosis of this disease, and to improve understanding of both the consequences of neutropenia and the benefits of treatment with granulocyte colony-stimulating factor (G-CSF). Recent findings In 88 patients with BTHS, neutropenia, that is, at least one count...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial: Update in myeloid biology
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

The role of genomics in transfusion medicine
Purpose of review To summarize recent advances in red blood cell (RBC) blood group genotyping, with an emphasis on advances in the use of NGS next generation sequencing (NGS) to detect clinically relevant blood group gene variation. Recent findings Genetic information is useful in predicting RBC blood group antigen expression in several clinical contexts, particularly, for patients at high-risk for allosensitization, such as multiple transfused patients. Blood group antigen expression is directed by DNA variants affecting multiply genes. With over 300 known antigens, NGS offers the attractive prospect of comprehensive...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Towards increasing shelf life and haemostatic potency of stored platelet concentrates
Purpose of review Platelet transfusion is a widely used therapy in treating or preventing bleeding and haemorrhage in patients with thrombocytopenia or trauma. Compared with the relative ease of platelet transfusion, current practice for the storage of platelets is inefficient, costly and relatively unsafe, with platelets stored at room temperature (RT) for upto 5–7 days. Recent findings During storage, especially at cold temperatures, platelets undergo progressive and deleterious changes, collectively termed the ‘platelet storage lesion’, which decrease their haemostatic function and posttransfusion...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

The clinical impact of glucose-6-phosphate dehydrogenase deficiency in patients with sickle cell disease
Purpose of review Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell disease (SCD) cause hemolysis, often occurring in individuals of African descent. These disorders co-occur frequently, and possibly interact, altering clinical outcomes in SCD. However, epidemiological investigations of SCD with G6PD deficiency have produced variable results. This contribution reviews the available data about the interaction of G6PD deficiency and SCD. Recent findings Overall, G6PD deficiency contributes few, if any, effects to laboratory values and clinical outcomes in SCD patients, but may impact transfusion effica...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Restoring antiviral immunity with adoptive transfer of ex-vivo generated T cells
Purpose of review Latent viruses such as cytomegalovirus (CMV), Epstein–Barr virus (EBV) and adenovirus (ADV) often reactivate in immunocompromised patients, contributing to poor clinical outcomes. A rapid reconstitution of antiviral responses via adoptive transfer of virus-specific T cells (VSTs) can prevent or eradicate even refractory infections. Here, we evaluate this strategy and the associated methodological, manufacturing and clinical advances. Recent findings From the early pioneering but cumbersome efforts to isolate CMV-specific T cell clones, new approaches and techniques have been developed to provid...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

‘Massive transfusion protocols and the use of tranexamic acid’
Purpose of review We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that specifically examine the use of TXA in massive transfusion protocols (MTPs), there are a few studies with subgroups of massive transfusion patients. Recent findings In recent years, many publications have discussed outcomes and safety associated with the addition of TXA to treatment plans for bleeding pediatric, trauma, and postpartum hemorrhage patients. In general, TXA appears to decrease mortality and transfusion requirements. Summary ...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Murine models of autoimmune hemolytic anemia
Purpose of review Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is known about the etiology and pathogenesis of AIHA has been learned from observations made in human patients and murine models, but many questions remain; importantly, it is still unclear why some people generate RBC-specific autoantibodies. The combination of technological advancements applied to existing models and the development of new AIHA murine models will continue to provide considerable insight into the initiation of AIHA and prov...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

To transfuse or not transfuse: an intensive appraisal of red blood cell transfusions in the ICU
Purpose of review This review is a critical appraisal of the current data comparing restrictive vs. liberal transfusion strategies for patients who are critically ill in ICUs. We focus on four subsets of critically ill patients: pediatric patients, patients with gastrointestinal bleeds, septic patients and patients undergoing cardiac surgery. Recent findings Almost a decade after the TRICC trial, a randomized trial showing the safety of a restrictive transfusion threshold in critically ill patients, four large randomized controlled trials have shown that a restrictive transfusion strategy is safe in pediatric critical...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention
Purpose of review The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events. Recent findings Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation. There have also been enhancements in understanding of what may contribute to...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?
Purpose of review After transfusion, a percentage of red blood cells undergo hemolysis within macrophages. Intravascular exposures to hemin and hemoglobin (Hb) can occur after storage bag hemolysis, some transfusion reactions, during use of medical assist devices and in response to bacterial hemolysins. Proteins that regulate iron, hemin and Hb either become saturated after iron excess (transferrin, Tf) or depleted after hemin (hemopexin, Hpx) and Hb (haptoglobin, Hp) excess. Protein saturation or stoichiometric imbalance created by transfusion increases exposure to non-Tf bound iron, hemin and Hb. Tf, Hpx and Hp are bei...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Current and future status of stem cell expansion
Purpose of review Herein, we seek to describe the current and future role of ex-vivo expansion of cord blood hematopoietic stem cells. Recent findings As this field is only in its infancy, there have been many challenges identified. Decreased number of stem cells contained in a cord blood unit and early differentiation of stem cells once expanded have been two overarching challenges faced by the field. Many recent techniques have focused on the properties of the microenvironment and targetable cellular pathways as novel approaches to circumvent these challenges. Summary Novel discoveries have led to the development...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Age-related clonal hematopoiesis: implications for hematopoietic stem cell transplantation
Purpose of review Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. Here we will review the implications of ARCH in the context of HSCT. Recent findings ARCH is highly prevalent in the general population and com...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Hematopoietic stem cell transplantation for autoimmune diseases: more than just prolonged immunosuppression
Purpose of review To summarize the current clinical experience in the use of autologous hematopoietic stem cell transplantation (HSCT) in autoimmune disease and to explore the concept of durable remission induction and tissue de-remodeling via restoration of normal niche function and “immune reset." Recent findings Controlled clinical trials in systemic sclerosis, multiple sclerosis, and Crohn's disease as well as extensive uncontrolled trial and registry data have established the unique role of HSCT in selected cases. Although HSCT for multiple sclerosis and systemic sclerosis has recently entered several ...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Next-generation sequencing-based minimal residual disease monitoring in patients receiving allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome
Purpose of review The monitoring of minimal residual disease (MRD) has important clinical implications in both the pre and postallogeneic stem cell transplant (SCT) setting in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Next-generation sequencing (NGS) is a rapidly improving technology whose application to the monitoring of MRD is an active area of research. We aim to describe existing methods of MRD in AML and MDS, with a focus on the utility of NGS in patients undergoing SCT. Recent findings Flow cytometry and quantitative PCR have been recommended by the European Leukemia Net as the preferred m...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Microtransplantation: clinical applications and mechanisms
Purpose of review Microtransplantation (MST) has been successfully used to manage patients with hematological malignancies, especially older patients with acute myeloid leukemia (AML). Recent clinical applications and mechanistic studies of MST are reviewed. Recent findings MST improves complete remission rates which have no significant difference among age groups in older patients with AML. Sufficient courses of postremission therapy lead to prolonged overall survival and reduced relapse rate. MST also benefits young patients with low-risk or intermediate-risk AML who lack a human leukocyte antigen-identical donor an...
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 5, 2018 Category: Hematology Tags: Editorial Introductions Source Type: research

Megakaryocyte modification of platelets in thrombocytopenia
Purpose of review Platelets are small, anucleate cells that circulate within the blood and play essential roles in preserving vascular integrity. However, abnormalities in either platelet production or destruction can result in thrombocytopenia, clinically defined by a platelet count lower than 150 000/μL of whole blood. Thrombocytopenia is frequently associated with impaired hemostatic responses to vascular injury and can be life-threatening because of bleeding complications. Megakaryocytes are the precursor cells responsible for platelet production, a process commonly referred to as thrombopoiesis. This review spe...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Factor XII in inflammation and wound healing
Purpose of review This review describes the contribution of coagulation factor XII (FXII) in sterile inflammation and wound healing, focusing on recently identified roles for zymogen FXII in neutrophil functions. Recent findings Recent studies have identified an important role for FXII in neutrophil trafficking. In particular, following neutrophil activation, autocrine FXII signals through the urokinase plasminogen activator receptor (uPAR) on the neutrophil surface to upregulate neutrophil functions. The sum of these activities leads to neutrophil adhesion, chemotaxis, and neutrophil extracellular (NET) formation. Do...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Multiple protein disulfide isomerases support thrombosis
Purpose of review The present review provides an overview of recent findings on new members of the protein disulfide isomerase (PDI) family required for thrombosis. Recent findings Twenty years ago PDI was shown to mediate platelet aggregation, and 10 years ago PDI was shown to support thrombosis in vivo. Subsequently, other members of this endoplasmic reticulum family of enzymes, ERp57 and ERp5, were demonstrated to support thrombosis. A fourth member, ERp72, was recently shown to be required for platelet accumulation and fibrin deposition in vivo. None of these enzymes can individually support these processes. Moreo...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

The plasma contact system as a modulator of innate immunity
Purpose of review The contact system is a plasma protease cascade, which activates the proinflammatory kallikrein–kinin system and the procoagulant intrinsic coagulation pathway. Recent advances demonstrating the novel functions of this system as a key player of innate immune system will be introduced in the present review. Recent findings The role of the contact system is to initiate and participate in pathophysiological responses to injury, mainly the processes of coagulation and inflammation. The past few years have seen substantial progress, showing a new role of this system in regulation of innate immunity....
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Emerging applications of aptamers for anticoagulation and hemostasis
Purpose of review Since the selection of the first thrombin-binding aptamer in 1992, the use of nucleic acid aptamers to target specific coagulation factors has emerged as a valuable approach for generating novel anticoagulant and procoagulant therapeutics. Herein, we highlight the most recent discoveries involving application of aptamers for those purposes. Recent findings Learning from the successes and pitfalls of the FIXa-targeting aptamer pegnivacogin in preclinical and clinical studies, the latest efforts to develop antidote-controllable anticoagulation strategies for cardiopulmonary bypass that avoid unfraction...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Pathophysiology of immune thrombocytopenia
Purpose of review Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder with as of yet, no established clinical prognostic or diagnostic biomarkers. Patients frequently experience a markedly decreased quality of life and may be at risk for severe/fatal haemorrhage. Here, we address discoveries in the pathogenesis of ITP, and novel therapeutic strategies in mouse models and human patients. Consolidation of these findings should be important in providing insight to establish future prognostic protocols as well as cutting-edge therapeutics to target refractory ITP. Recent findings It is unknown why a sig...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Tolerance induction in hemophilia: innovation and accomplishments
Purpose of review Hemophilia is an X-linked blood coagulation genetic disorder, which can cause significant disability. Replacement therapy for coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) may result in the development of high-affinity alloantibodies (’inhibitors’) to the replacement therapy, thus making it ineffective. Therefore, there is interest in directing immunological responses towards tolerance to infused factors. Recent findings In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of ...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Fibrinogen and factor XIII: newly recognized roles in venous thrombus formation and composition
Purpose of review In spite of significant morbidity and mortality associated with venous thromboembolism, the underlying pathogenesis remains poorly understood. Recent findings Clues to operant pathogenic mechanisms are found in the unique morphology and composition of these thrombi, which have substantial red blood cell and fibrin content. Recent studies have revealed biochemical and biophysical mechanisms that dictate fibrin structure in venous thrombi and promote retention of red blood cells within the contracted clots. These mechanisms include newly recognized contributions of fibrin network structure and factor X...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Subverting bradykinin-evoked inflammation by co-opting the contact system: lessons from survival strategies of Trypanosoma cruzi
Purpose of review During Chagas disease, Trypanosoma cruzi alternates between intracellular and extracellular developmental forms. After presenting an overview about the roles of the contact system in immunity, I will review experimental studies showing that activation of the kallikrein-kinin system (KKS) translates into mutual benefits to the host/parasite relationship. Recent findings T. cruzi trypomastigotes initiate inflammation by activating tissue-resident innate sentinel cells via the TLR2/CXCR2 pathway. Following neutrophil-evoked microvascular leakage, the parasite's major cysteine protease (cruzipain) cleave...
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 3, 2018 Category: Hematology Tags: Editorial Introduction Source Type: research