When should patients receive consolidation chemotherapy before allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission?
Purpose of review Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT. Recent findings Randomized controlled studies are lacking. Data derive largely from four large retrospective registry studies. These analyses are consistent in demonstrating the lack of any survival ...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions
We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including ‘7+3 Plus’ combinations. Summary Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrat...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Cohesin mutations in myeloid malignancies made simple
Purpose of review Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer Recent findings The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division. Although initially...
Source: Current Opinion in Hematology - February 1, 2018 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, 2018 Category: Hematology Tags: Editorial Introduction Source Type: research

Metabolic regulation of macrophages in tumor microenvironment
Purpose of review Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. Recent findings Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells. However, the Warburg effect has recently been proven to exist in various types of immune cells in ...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

The regulation and importance of monocyte chemoattractant protein-1
Purpose of review Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition. Recent findings Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/mac...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Dysregulated myelopoiesis and hematopoietic function following acute physiologic insult
Purpose of review The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. Recent findings Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term fu...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity
Purpose of review Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Recent findings Although agranulocytosis and cutaneous vasculitis...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring
Purpose of review Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species – nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed. Recent findings The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine &nd...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae
Purpose of review Gonorrhea is a major global health concern, caused by the bacterium Neisseria gonorrhoeae. The main clinical feature of acute gonorrhea is neutrophilic influx that is unable to clear infection. Women of reproductive age are predominantly at risk for serious sequelae of gonorrhea, including pelvic inflammatory disease, ectopic pregnancy, and infertility. This review will highlight how neutrophils are recruited to the female reproductive tract (FRT) in response to N. gonorrhoeae, how N. gonorrhoeae resists killing by neutrophils, and the connection between neutrophilic inflammation and cellular damage. R...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Long-term observational studies of chronic granulomatous disease
Purpose of review Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients. Recent findings For years, CGD is a known cause of life-threatening infections...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Green neutrophilic inclusions: current understanding and review of literature
Purpose of review Green cytoplasmic inclusions in neutrophils are an uncommon finding on the peripheral blood smear. A comprehensive review of the literature is presented here with the goal of summarizing knowledge to date and increasing awareness. Recent findings A total of 41 cases have been reported in the literature, indicating the rarity of these green neutrophilic inclusions. Clinically, the inclusions have most consistently been associated with elevated transaminases, hepatic failure, and a high early mortality rate. The precise composition of the inclusions has not been confirmed. Summary Clinicians, hemato...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial: myeloid biology issue 2018
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 1, 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 - January 1, 2018 Category: Hematology Tags: Editorial Introductions Source Type: research

Metabolic regulation of macrophages in tumor microenvironment
Purpose of review Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. Recent findings Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells. However, the Warburg effect has recently been proven to exist in various types of immune cells in ...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

The regulation and importance of monocyte chemoattractant protein-1
Purpose of review Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition. Recent findings Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/mac...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Dysregulated myelopoiesis and hematopoietic function following acute physiologic insult
Purpose of review The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. Recent findings Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term fu...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity
Purpose of review Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Recent findings Although agranulocytosis and cutaneous vasculitis...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring
Purpose of review Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species – nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed. Recent findings The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine &nd...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae
Purpose of review Gonorrhea is a major global health concern, caused by the bacterium Neisseria gonorrhoeae. The main clinical feature of acute gonorrhea is neutrophilic influx that is unable to clear infection. Women of reproductive age are predominantly at risk for serious sequelae of gonorrhea, including pelvic inflammatory disease, ectopic pregnancy, and infertility. This review will highlight how neutrophils are recruited to the female reproductive tract (FRT) in response to N. gonorrhoeae, how N. gonorrhoeae resists killing by neutrophils, and the connection between neutrophilic inflammation and cellular damage. R...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Long-term observational studies of chronic granulomatous disease
Purpose of review Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients. Recent findings For years, CGD is a known cause of life-threatening infections...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Green neutrophilic inclusions: current understanding and review of literature
Purpose of review Green cytoplasmic inclusions in neutrophils are an uncommon finding on the peripheral blood smear. A comprehensive review of the literature is presented here with the goal of summarizing knowledge to date and increasing awareness. Recent findings A total of 41 cases have been reported in the literature, indicating the rarity of these green neutrophilic inclusions. Clinically, the inclusions have most consistently been associated with elevated transaminases, hepatic failure, and a high early mortality rate. The precise composition of the inclusions has not been confirmed. Summary Clinicians, hemato...
Source: Current Opinion in Hematology - November 29, 2017 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial: myeloid biology issue 2018
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 29, 2017 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 29, 2017 Category: Hematology Tags: Editorial Introductions Source Type: research

Current status of blood ‘pharming’: megakaryoctye transfusions as a source of platelets
Purpose of review: Donor-derived platelets have proven to be of hemostatic value in many clinical settings. There is a fear that the need for platelets may outgrow the donor pool in first-world countries. Moreover, there are other challenges with donor platelets that add to the impetus to find an alternative platelet source, especially after the megakaryocyte cytokine thrombopoietin was identified. Megakaryocytes have since been differentiated from numerous cell sources and the observed released platelet-like particles (PLPs) have led to calls to develop such products for clinical use. The development of megakaryocytes fro...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Is there a standard-of-care for transfusion therapy in thalassemia?
Purpose of review: Thalassemia is the most common form of inherited anemia, characterized by variable clinical phenotypes. The purpose of this review is to summarize the transfusion support in thalassemia patients and the management of transfusion-related iron overload. Recent findings: The most recent evidence on transfusion strategy and iron chelation therapy in thalassemia arising from clinical trials as well as from recommendation guidelines are critically discussed. Summary: Enhancements in the global care of thalassemia, resulting from the combination of an appropriate transfusion approach and iron chelation therap...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Transfusion-related immunomodulation: a reappraisal
Purpose of review: This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing ‘pure’ red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the ‘storage lesion.’ Macrophages are a key cell type involved in physiological and pathological RBC c...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Genotyping to prevent Rh disease: has the time come?
Purpose of review: In this review, we analyzed the current literature on noninvasive fetal RHD typing to answer the question whether the administration of RhIg to prevent D-alloimmunization during pregnancy can be safely guided by fetal RHD typing. Recent findings: Recently the first centers that implemented large-scale nationwide fetal RHD typing in the second trimester for targeted RhIg administration have published their studies evaluating the diagnostic accuracy of their screening programs. These data show that fetal RHD typing in a routine setting is, at least in a population of European descent, accurate enough to g...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?
Purpose of review: This review aims to highlight recent advances in our understanding of how anti-red blood cell (RBC) antibodies prevent erythrocyte immunization with an emphasis on new murine models. Recent findings: New murine models with clinically relevant human erythrocyte antigens have been used to understand the alloimmunization process and its inhibition. The search to elucidate the mechanism of action of IgG-mediated inhibition of erythrocyte alloimmunization has provided new evidence in support of a potential role for epitope masking, immune deviation and/or antigen modulation in this process. In addition, rece...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Prehospital hemostatic resuscitation to achieve zero preventable deaths after traumatic injury
Purpose of review: To describe how hemostatic resuscitation can be used in the prehospital phase of resuscitation to reduce preventable deaths after traumatic injury. Recent findings: Hemorrhagic shock is the leading cause of death that is preventable after injury. The National Academy of Sciences, recently, recommended that achievement of zero preventable deaths after traumatic injury should be the goal of a national trauma system. In the United States, there are an estimated 25 000 preventable deaths per year in the prehospital phase of resuscitation because of traumatic hemorrhagic shock. Therefore, to achieve the go...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Novel therapeutic approaches for thrombotic thrombocytopenic purpura
This study reviews emerging therapies for thrombotic thrombocytopenic purpura. Recent findings: Studies indicate that reducing anti-ADAMTS13 antibody levels through B-cell depletion or proteasome inhibition is effective for the management of refractory disease. Preliminary reports examining anti-CD20 therapy for the treatment of initial disease or as maintenance therapy for seropositive patients suggest the addition of immunosuppression in other disease phases may delay relapse. Exciting developments in targeted therapies to von Willebrand Factor and recombinant ADAMTS13 hold promise for transforming disease management. ...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Is there a standard-of-care for transfusion support of patients with haematological malignancies?
Purpose of review: Patients with haematological malignancies are a high-user group for blood transfusions. Here, we describe the current evidence on transfusion policies in patients with haematological malignancies, based on recent systematic reviews of RCTs. Recent findings: Results from six RCTs (1195 participants) suggest that prophylactic platelet transfusions reduce bleeding compared with therapeutic-only use, although the effects varied according to patient diagnosis/treatment plan. A meta-analysis of seven RCTs (1814 participants) reported that low-dose platelet transfusions (1.1 × 1011/m2 ± 25...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Hematopoietic cell transplantation for aplastic anemia
Purpose of review: Improvements in allogeneic hematopoietic cell transplantation (HCT) with better donor selection, conditioning regimens and graft vs. host disease prophylaxis make it reasonable to move HCT earlier in the algorithm for management of severe aplastic anemia (SAA). Recent progress in transplantation is reviewed whereas issues related to developing countries are also addressed. Recent findings: Multiple research centers are reporting on clonality, mutations and telomere disorders in SAA, which may help to choose the most appropriate therapy upfront. Eltrombopag, in combination with immunosuppressive therapy ...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Autologous hematopoietic cell transplantation of mantle cell lymphoma: emerging trends
Purpose of review: The management of mantle cell lymphoma has changed significantly with the adoption of immunochemotherapy and dose intensive treatment strategies in specific patient populations. Randomized controlled trials have established the role of rituximab-based treatments and autologous stem cell transplantation as standards of care. Novel therapeutics are also being integrated into these treatment strategies. Recent findings: Rituximab-based primary treatment has been shown to significantly improve complete remission rates. The addition of autologous stem cell transplantation has also improved progression-free s...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Medical and policy considerations for nuclear and radiation accidents, incidents and terrorism
Purpose of review: The purpose of this review is to address the increasing medical and public concern regarding the health consequences of radiation exposure, a concern shaped not only by fear of another Chernobyl or Fukushima nuclear power facility accident but also by the intentional use of a nuclear weapon, a radiological dispersion device, a radiological exposure device, or an improved nuclear device by rogue states such as North Korea and terrorist organizations such as Al Qaeda and ISIS. Recent findings: The United States has the medical capacity to respond to a limited nuclear or radiation accident or incident but ...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

The importance of natural killer cell killer immunoglobulin-like receptor-mismatch in transplant outcomes
Purpose of review: In recent years, the rules of engagement between natural killer (NK) cells and their targets have become better defined with the identification of an array of NK surface molecules, notably the killer immunoglobulin-like (KIR) receptors and their ligands on target cells through which signals of activation or suppression of NK function are mediated. After allogeneic stem cell transplantation (SCT), the opportunity for NK cell activation can occur both in human leucocyte antigen (HLA) matched and HLA mismatched pairs. Although less well explored in HLA identical transplants, many studies confirm the importa...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

The changing landscape of gene editing in hematopoietic stem cells: a step towards Cas9 clinical translation
Purpose of review: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment...
Source: Current Opinion in Hematology - October 7, 2017 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research

Allogeneic stem-cell transplantation for myelofibrosis
Purpose of review: Allogeneic hematopoietic stem-cell transplantation (HSCT) remains the only curative therapy for myelofibrosis. The number of HSCTs performed for this indication has been steadily increasing over the past years, even after the approval of the Janus kinase (JAK) inhibitor, ruxolitinib. This increase may be attributed to improved patient selection based on new prognostic molecular markers, more frequent use of matched unrelated donors, secondary to better (high-resolution) human leukocyte antigen typing and supportive care. Ruxolitinib approval raises new questions regarding the role of JAK inhibitors in th...
Source: Current Opinion in Hematology - October 7, 2017 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 7, 2017 Category: Hematology Tags: Editorial Introductions Source Type: research

The ins and outs of endocytic trafficking in platelet functions
Purpose of review: Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance is poorly understood as is its mechanism. The present review discusses the current understanding of platelet endocytosis and its implications for platelet function. Recent findings: Recent studies are beginning to identify and define the proteins that mediate platelet endocytosis. These studies have shown that platelets contain different endosomal compartments and may use multiple endocytic routes to take in circulating molecules and surf...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Ser/Thr protein kinase Bβ-NADPH oxidase 2 signaling in thromboinflammation
Purpose of review: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)β-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. Recent findings: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding
Purpose of review: New therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future development prospects. Recent findings: Underlying many procoagulant therapeutic approaches is the rapid generation of thrombin to promote robust clot formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide effective hemostasis to mitigate bleeding in hemophilia and other clinical situations. Over the past decade, we explored the possibility of using zymoge...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Targeting activated protein C to treat hemophilia
Purpose of review: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia. Recent findings: A serpin (serine protease inhibitor) was engineered to specifi...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Advances in vascular thiol isomerase function
Purpose of review: The present review will provide an overview of several recent advances in the field of vascular thiol isomerase function. Recent findings: The initial observation that protein disulfide isomerase (PDI) functions in thrombus formation occurred approximately a decade ago. At the time, there was little understanding regarding how PDI or other vascular thiol isomerases contribute to thrombosis. Although this problem is far from solved, the past few years have seen substantial progress in several areas that will be reviewed in this article. The relationship between PDI structure and its function has been inv...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Angiopoietins and Tie2 in vascular inflammation
Purpose of review: As a subset of the organism-wide reaction to severe infection, the host vascular response has received increasing attention in recent years. The transformation that small blood vessels undergo to facilitate the clearance of pathogens may become harmful to the host if it occurs too broadly or if it is sustained too long. Adverse clinical manifestations of leaky and inflamed blood vessels include edema impairing the function of critical organs and circulatory shock. Recent findings: The study suggests that this host vascular response may be both measurable and potentially targetable. Tie2 is a receptor ty...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease
Purpose of review: To review the evidence that the Alzheimer peptide β-amyloid interacts with the blood coagulation system and influences the pathophysiology of the disease. Recent findings: β-amyloid can interact with fibrinogen and blood coagulation factor XII and trigger ischemia and inflammation. Summary: β-amyloid interacts with fibrinogen and factor XII. These interactions can lead to increased clotting, abnormal clot formation, persistent fibrin deposition, and generation of proinflammatory molecules. These events can damage neurons and could contribute to the cognitive decline in Alzheimer's diseas...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Novel targets for anticoagulants lacking bleeding risk
Purpose of review: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites. As a result currently used anticoagulants substantially raise the risk of bleeding and are associated with an increase in p...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Single-chain factor XII: a new form of activated factor XII
Purpose of review: Exposure of blood to foreign surfaces induces reciprocal conversion of the plasma proteins factor XII (fXII) and plasma prekallikrein (PPK) to the proteases α-fXIIa and α-kallikrein. This process, called contact activation, has a range of effects on host defence mechanisms, including promoting coagulation. The nature of the triggering mechanism for contact activation is debated. One hypothesis predicts that fXII has protease activity, either intrinsically or upon surface-binding, that initiates contact activation. We tested this by assessing the proteolytic activity of a recombinant fXII vari...
Source: Current Opinion in Hematology - August 3, 2017 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Introduction to current issue
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 3, 2017 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, 2017 Category: Hematology Tags: Editorial Introduction Source Type: research