1,912 results match your criteria Current Opinion in Hematology[Journal]


Novel Approaches for Systemic Mastocytosis.

Curr Opin Hematol 2019 Mar;26(2):112-118

Knight Cancer Institute.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000486DOI Listing
March 2019
4 Reads

Editorial introduction.

Authors:

Curr Opin Hematol 2019 Mar;26(2)

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http://dx.doi.org/10.1097/MOH.0000000000000487DOI Listing
March 2019
1 Read

Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective?

Curr Opin Hematol 2019 Mar;26(2):71-76

Department of Medicine, Division of Hematology, University of Colorado, Aurora, Colorado, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000485DOI Listing
March 2019
4 Reads

Luke Fletcher, md1,2 and uma borate, md1,2.

Curr Opin Hematol 2019 Jan 11. Epub 2019 Jan 11.

Knight Cancer Institute.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000486DOI Listing
January 2019
2 Reads

Progress in the problem of relapsed or refractory acute myeloid leukemia.

Curr Opin Hematol 2019 Mar;26(2):88-95

Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000490DOI Listing
March 2019
2 Reads

What are the most promising new agents in myelodysplastic syndromes?

Curr Opin Hematol 2019 Mar;26(2):77-87

Smilow Cancer Center at Yale New Haven Hospital, New Haven, Connecticut, USA.

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 in low-risk groups and preventing progression of disease to acute myeloid leukemia in high-risk groups. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000483DOI Listing
March 2019
6 Reads

Posttransplant maintenance therapy for acute leukemias.

Curr Opin Hematol 2019 Mar;26(2):96-111

Stem Cell Transplant Program, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000484DOI Listing
March 2019
4 Reads

Novel tyrosine kinase inhibitors for patients with inadequate response in chronic myeloid leukemia.

Authors:
Michael J Mauro

Curr Opin Hematol 2019 Mar;26(2):119-123

Myeloproliferative Neoplasms Program, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

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 with the promise of greater selectivity and better adverse event profile. In addition, alternate approaches to ABL1 inhibition, targeting the myristoyl pocket of ABL1, are showing promising early results and are moving into later phase trials. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000489DOI Listing
March 2019
2 Reads

Shifting therapeutic paradigms in induction and consolidation for older adults with acute myeloid leukemia.

Curr Opin Hematol 2019 Mar;26(2):51-57

Department of Hematology and Bone Marrow Transplantation, Rambam Healthcare Campus.

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 to this patient population that can predict individual fitness to treatment, refined knowledge of the unique mutational landscape, and incorporating new combinations and novel agents designed to target the AML biology. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000480DOI Listing
March 2019
2 Reads

Outpatient induction and consolidation care strategies in acute myeloid leukemia.

Curr Opin Hematol 2019 Mar;26(2):65-70

Division of Hematology, Department of Medicine.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000481DOI Listing
March 2019
2 Reads

Which patients with acute myeloid leukemia in CR1 can be spared an allogeneic transplant?

Curr Opin Hematol 2019 Mar;26(2):58-64

Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, USA.

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 outcome if treated with chemotherapy alone is good enough to spare them the risks associated with allo-SCT. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000482DOI Listing
March 2019
19 Reads

Editorial: Update in myeloid biology.

Authors:
David C Dale

Curr Opin Hematol 2019 Jan;26(1):1-5

Department of Medicine, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1097/MOH.0000000000000475DOI Listing
January 2019
1 Read

Cell biology of activated protein C.

Curr Opin Hematol 2019 Jan;26(1):41-50

Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000473DOI Listing
January 2019
8 Reads

Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor.

Curr Opin Hematol 2019 Jan;26(1):16-21

Department of Pediatrics, Glycogen Storage Disease Program, Connecticut Children's Medical Center, Hartford, Connecticut, USA.

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). Read More

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http://dx.doi.org/10.1097/MOH.0000000000000474DOI Listing
January 2019
13 Reads

Neutropenia in Barth syndrome: characteristics, risks, and management.

Curr Opin Hematol 2019 Jan;26(1):6-15

Department of Medicine, University of Washington, Seattle, Washington, USA.

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). Read More

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http://dx.doi.org/10.1097/MOH.0000000000000472DOI Listing
January 2019
14 Reads

Mechanisms of leukemic transformation in congenital neutropenia.

Authors:
Daniel C Link

Curr Opin Hematol 2019 Jan;26(1):34-40

Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000479DOI Listing
January 2019
9 Reads

The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics.

Curr Opin Hematol 2019 Jan;26(1):28-33

Department of Pathology, Harvard Medical School.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000476DOI Listing
January 2019
12 Reads

The clinical consequences of neutrophil priming.

Curr Opin Hematol 2019 Jan;26(1):22-27

Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000471DOI Listing
January 2019
13 Reads

Towards increasing shelf life and haemostatic potency of stored platelet concentrates.

Curr Opin Hematol 2018 Nov;25(6):500-508

Hoxworth Blood Center, University of Cincinnati Academic Health Center.

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 survival. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000456DOI Listing
November 2018
18 Reads

Restoring antiviral immunity with adoptive transfer of ex-vivo generated T cells.

Curr Opin Hematol 2018 Nov;25(6):486-493

Columbia Center for Translational Immunology (CCTI), Division of Hematology/Oncology, Columbia University Medical Center, New York, New York, USA.

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. Read More

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http://Insights.ovid.com/crossref?an=00062752-900000000-9930
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http://dx.doi.org/10.1097/MOH.0000000000000461DOI Listing
November 2018
27 Reads

To transfuse or not transfuse: an intensive appraisal of red blood cell transfusions in the ICU.

Curr Opin Hematol 2018 Nov;25(6):468-472

Harvard Medical School, Laboratory and Transfusion Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000460DOI Listing
November 2018
3 Reads

When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?

Curr Opin Hematol 2018 Nov;25(6):452-458

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000458DOI Listing
November 2018
3 Reads

Next-generation sequencing-based minimal residual disease monitoring in patients receiving allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome.

Curr Opin Hematol 2018 Nov;25(6):425-432

Allogeneic Blood and Marrow Transplant Program, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

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. Read More

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http://Insights.ovid.com/crossref?an=00062752-900000000-9930
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http://dx.doi.org/10.1097/MOH.0000000000000464DOI Listing
November 2018
6 Reads

Current and future status of stem cell expansion.

Curr Opin Hematol 2018 Nov;25(6):446-451

Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000463DOI Listing
November 2018
1 Read

The clinical impact of glucose-6-phosphate dehydrogenase deficiency in patients with sickle cell disease.

Curr Opin Hematol 2018 Nov;25(6):494-499

Laboratory of Transfusion Biology, Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000455DOI Listing
November 2018
10 Reads

Murine models of autoimmune hemolytic anemia.

Curr Opin Hematol 2018 Nov;25(6):473-481

BloodworksNW Research Institute.

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 provide a platform for the design of more effective therapies. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200381PMC
November 2018
15 Reads

Hematopoietic stem cell transplantation for autoimmune diseases: more than just prolonged immunosuppression.

Authors:
Alan Tyndall

Curr Opin Hematol 2018 Nov;25(6):433-440

Department of Rheumatology, University Hospital, Basel, Switzerland.

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 official treatment guidelines, mechanistic studies are few but indicate some possible modes of action, for example, increase of regulatory T cells. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000466DOI Listing
November 2018
14 Reads

Microtransplantation: clinical applications and mechanisms.

Curr Opin Hematol 2018 Nov;25(6):417-424

Department of Hematology and Transplantation, The 307th Hospital of Chinese People's Liberation Army, Beijing, China.

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. Read More

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http://Insights.ovid.com/crossref?an=00062752-900000000-9929
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http://dx.doi.org/10.1097/MOH.0000000000000470DOI Listing
November 2018
14 Reads

The role of genomics in transfusion medicine.

Curr Opin Hematol 2018 Nov;25(6):509-515

Bloodworks Northwest Research Institute.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000469DOI Listing
November 2018
3 Reads

Age-related clonal hematopoiesis: implications for hematopoietic stem cell transplantation.

Curr Opin Hematol 2018 Nov;25(6):441-445

Princess Margaret Cancer Centre, University Health Network (UHN).

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000465DOI Listing
November 2018
17 Reads

'Massive transfusion protocols and the use of tranexamic acid'.

Curr Opin Hematol 2018 Nov;25(6):482-485

Columbia University Irving Medical Center, New York, New York, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000457DOI Listing
November 2018
13 Reads

Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention.

Curr Opin Hematol 2018 Nov;25(6):459-467

Department of Laboratory Medicine, Yale School of Medicine.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000462DOI Listing
November 2018
18 Reads

Editorial introduction.

Authors:

Curr Opin Hematol 2018 Sep;25(5)

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http://dx.doi.org/10.1097/MOH.0000000000000454DOI Listing
September 2018
1 Read

The plasma contact system as a modulator of innate immunity.

Authors:
Yi Wu

Curr Opin Hematol 2018 Sep;25(5):389-394

The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000448DOI Listing
September 2018
5 Reads

Subverting bradykinin-evoked inflammation by co-opting the contact system: lessons from survival strategies of Trypanosoma cruzi.

Curr Opin Hematol 2018 Sep;25(5):347-357

Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Center of Health Sciences (CCS), Cidade Universitária, Rio de Janeiro, Brazil.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000444DOI Listing
September 2018
12 Reads

Emerging applications of aptamers for anticoagulation and hemostasis.

Curr Opin Hematol 2018 Sep;25(5):382-388

Department of Pharmacology and Cancer Biology.

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 unfractionated heparin involve potentiation of the exosite-binding factor X (FX)a aptamer 11F7t by combination with either a small molecule FXa catalytic site inhibitor or a thrombin aptamer. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000452DOI Listing
September 2018
3 Reads

Pathophysiology of immune thrombocytopenia.

Curr Opin Hematol 2018 Sep;25(5):373-381

Department of Laboratory Medicine and Pathobiology.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000447DOI Listing
September 2018
3 Reads

Factor XII in inflammation and wound healing.

Authors:
Evi X Stavrou

Curr Opin Hematol 2018 Sep;25(5):403-409

Department of Medicine, Louis Stokes Veterans Administration Medical Center.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000450DOI Listing
September 2018
1 Read

Multiple protein disulfide isomerases support thrombosis.

Authors:
David W Essex Yi Wu

Curr Opin Hematol 2018 Sep;25(5):395-402

Department of Medicine, Division of Hematology, Sol Sherry Thrombosis Center, Temple University, Philadelphia, Pennsylvania, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000449DOI Listing
September 2018
3 Reads

Tolerance induction in hemophilia: innovation and accomplishments.

Curr Opin Hematol 2018 Sep;25(5):365-372

Department Pediatrics, Indiana University, Indianapolis, Indiana, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000446DOI Listing
September 2018
11 Reads

Fibrinogen and factor XIII: newly recognized roles in venous thrombus formation and composition.

Authors:
Alisa S Wolberg

Curr Opin Hematol 2018 Sep;25(5):358-364

Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215450PMC
September 2018
5 Reads

Megakaryocyte modification of platelets in thrombocytopenia.

Curr Opin Hematol 2018 Sep;25(5):410-415

Division of Hematology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Harvard Institutes of Medicine, Boston, Massachusetts, USA.

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. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000451DOI Listing
September 2018
6 Reads

Exosomes in acute myeloid leukemia inhibit hematopoiesis.

Curr Opin Hematol 2018 Jul;25(4):279-284

Pathology, Immunology and Otolaryngology, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.

Purpose Of Review: Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML).

Recent Findings: Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000439DOI Listing
July 2018
2 Reads

Transcription factors FOXO in the regulation of homeostatic hematopoiesis.

Curr Opin Hematol 2018 Jul;25(4):290-298

Department of Cell, Developmental and Regenerative Biology.

Purpose Of Review: Work in the past decade has revealed key functions of the evolutionary conserved transcription factors Forkhead box O (FOXO) in the maintenance of homeostatic hematopoiesis. Here the diverse array of FOXO functions in normal and diseased hematopoietic stem and progenitor cells is reviewed and the main findings in the past decade are highlighted. Future work should reveal FOXO-regulated networks whose alterations contribute to hematological disorders. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000441DOI Listing
July 2018
7 Reads

Microenvironment signaling driving lymphomagenesis.

Curr Opin Hematol 2018 Jul;25(4):335-345

UMR_S 1236, Université Rennes 1, INSERM, Etablissement Français du Sang, Labex IGO.

Purpose Of Review: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment.

Recent Findings: Lymphoma supportive niche integrates a dynamic and orchestrated network of immune and stromal cell subsets producing, with a high level of spatial and kinetic heterogeneity, extracellular and membrane factors regulating tumor migration, survival, proliferation, immune escape, as well as tumor microarchitecture, and mechanical constraints. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000440DOI Listing
July 2018
1 Read

Precision medicine and lymphoma.

Curr Opin Hematol 2018 Jul;25(4):329-334

Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.

Purpose Of Review: The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment.

Recent Findings: DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000437DOI Listing
July 2018
3 Reads

SOX11, a key oncogenic factor in mantle cell lymphoma.

Curr Opin Hematol 2018 Jul;25(4):299-306

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona.

Purpose Of Review: SOX11 has emerged as a key transcription factor in the pathogenesis of mantle cell lymphoma (MCL) whereas it is not expressed in normal B cells or virtually in any other mature B-cell neoplasm. This review will examine the role of SOX11 as a biomarker in MCL, the new information on its transcriptional targets, and the mechanisms regulating its expression in MCL.

Recent Findings: SOX11 is highly expressed in conventional MCL, including cyclin D1-negative cases, but it is not expressed in the indolent leukemic nonnodal MCL subtype. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000434DOI Listing
July 2018
3 Reads

Genetic convergence of rare lymphomas.

Curr Opin Hematol 2018 Jul;25(4):307-314

Cancer Genetics and Genomics Program, Duke Cancer Institute, Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.

Purpose Of Review: We review the genetic foundations of different rare lymphomas to examine their shared origins. These data indicate the potential application of genomics to improve the diagnosis and treatment of these rare diseases.

Recent Findings: Next generation sequencing technologies have provided an important window into the genetic underpinnings of lymphomas. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000435DOI Listing
July 2018
4 Reads

The crosstalk between hematopoietic stem cells and their niches.

Curr Opin Hematol 2018 Jul;25(4):285-289

Sorbonne Université, Institut de Biologie Paris-Seine, CNRS UMR 7622, Inserm U1156, Laboratoire de Biologie du Développement, Paris, France.

Purpose Of Review: Hematopoietic stem cells (HSCs) reside in specific microenvironments also called niches that regulate HSC functions. Understanding the molecular and cellular mechanisms involved in the crosstalk between HSCs and niche cells is a major issue in stem cell biology and regenerative medicine. The purpose of this review is to discuss recent advances in this field with particular emphasis on the transcriptional landscape of HSC niche cells and the roles of extracellular vesicles (EVs) in the dialog between HSCs and their microenvironments. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000438DOI Listing
July 2018
2 Reads

Three-dimensional genome organization in normal and malignant haematopoiesis.

Curr Opin Hematol 2018 Jul;25(4):323-328

Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.

Purpose Of Review: The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer-promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners. Read More

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http://dx.doi.org/10.1097/MOH.0000000000000436DOI Listing
July 2018
3 Reads