The cause and pathogenesis of hemolytic transfusion reactions in sickle-cell disease
Purpose of review The current review aims to summarize the epidemiology, cause, pathophysiology, and management of hemolytic transfusion reactions in sickle-cell disease (SCD). Recent findings Patients undergoing occasional, isolated transfusions have been shown to have a higher risk of developing this condition. Despite the identification of well known risk factors, including alloimmunization, the pathophysiology of this syndrome remains unclear, as very severe forms with hyperhemolysis may develop in the absence of detectable antibodies, or with antibodies that are not considered to be clinically significant. Comple...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Banking with precision: transfusion medicine as a potential universal application in clinical genomics
Purpose of review To summarize the most recent scientific progress in transfusion medicine genomics and discuss its role within the broad genomic precision medicine model, with a focus on the unique computational and bioinformatic aspects of this emergent field. Recent findings Recent publications continue to validate the feasibility of using next-generation sequencing (NGS) for blood group prediction with three distinct approaches: exome sequencing, whole genome sequencing, and PCR-based targeted NGS methods. The reported correlation of NGS with serologic and alternative genotyping methods ranges from 92 to 99%. NGS ...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Transfusion support and alternatives for Jehovah's Witness patients
Purpose of review Jehovah's Witness patients with critical anemia or undergoing major surgery are challenging for healthcare providers to manage, as most will decline transfusion of whole blood and its main components. Recent advances in our understanding of hemostatic agents, alternative hemoglobin-based oxygen carriers, and patient blood management have culminated in a complex array of options to manage critical anemia and bleeding in this patient population. Recent findings Refusal of blood products in the setting of critical anemia is associated with significant risk of morbidity and mortality. With implementation...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Neonatal and pediatric platelet transfusions: current concepts and controversies
Purpose of review In this review, we focus on three specific concepts related to platelet transfusion in the neonatal and pediatric population: choice of transfusion threshold; use of ABO-mismatched platelets; transfusion of pathogen-reduced or inactivated platelets. Recent findings Recent trials support the use of lower platelet transfusion thresholds (25 000/μl) in preterm neonates, although data is limited to guide transfusion among more mature neonates. In children, there is low-level evidence as to what the prophylactic platelet transfusion threshold should be in many situations of thrombocytopenia, revealin...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

The 2019 guidelines from the American Society for Apheresis: what's new?
Purpose of review For over 30 years, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. These guidelines are periodically reviewed with the addition of new indications, retirement of some former indications and the provision of updated recommendations for current indications based on new published literature. During the last 12 years, updated guidelines have been published every 3 years to provide a reflection of current evidence-based apheresis practice. Recently, the eighth special issue was published....
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Can molecular markers of oxygen homeostasis and the measurement of tissue oxygen be leveraged to optimize red blood cell transfusions?
Purpose of review The clinical indication for transfusing red blood cells (RBCs) is to restore or maintain adequate oxygenation of respiring tissue. Oxygen (O2) transport, delivery, and utilization following transfusion are impacted by perfusion, hemoglobin (Hb) allosteric saturation/desaturation, and the concentration of tissue O2. Bioavailable O2 maintains tissue utilization and homeostasis; therefore, measuring imbalances in supply and demand could be valuable to assessing blood quality and transfusion effectiveness. O2 homeostasis is critically intertwined with erythropoietic response in blood loss and anemia and the...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Hematopoietic stem cell transplantation and cellular therapy in sickle cell disease: where are we now?
This study reviews the current status of allo-HCT and autologous cellular therapies for SCD. Recent findings Alternative sources of allogeneic stem cells from unmatched donors such as cord blood and haploidentical donors are gaining traction. Early experience has shown that better conditioning regimens and graft-versus-host disease prophylaxis are needed before these donor sources can gain widespread use. Clinical trials are underway to determine the feasibility and efficacy of autologous transplantation with gene modified hematopoietic stem cells. Gene therapy strategies include HbS gene correction, gene addition, and ...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

The controversial role of red cell transfusions for sickle cell pain
Purpose of review Red cell transfusions are one of the most common and important therapies used for patients with sickle cell disease (SCD). For prevention of strokes, there is abundant evidence that transfusions are efficacious, whereas for other indications, such as prevention of pain, there are less data. Nonetheless, with few therapeutic options, the use of transfusion for prevention of acute pain has increased in children and adults with SCD without a clear understanding of its benefits. Recent findings Although it makes conceptual sense that red cell transfusions would prevent pain that arises from vaso-occlusio...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Mechanisms of alloimmunization in sickle cell disease
Purpose of review Red blood cell (RBC) transfusion is an important treatment for some complications of sickle cell disease (SCD). On the contrary, transfusion may lead to alloimmunization to RBC antigens, with such alloantibodies putting patients at risk for acute or delayed hemolysis, and increasing the difficulty of finding compatible RBCs. Patients with SCD are more susceptible to developing RBC alloantibodies than other multiply transfused patient populations, for reasons that are not completely understood. In this review, we summarize the available data about risk factors and underlying mechanisms associated with RB...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik Source Type: research

Mechanisms of failure of chimeric antigen receptor T-cell therapy
Purpose of review Although chimeric antigen receptor T (CART)-cell therapy is best recognized for its antitumor effect in relapsed/refractory B-cell hematological cancers, it is still associated with a high relapse rate. Recent findings We firstly analyzed internal immunological and genetic reasons of CD19+ relapse after treatment for R/R B-cell hematological cancers with CART19 cells. The reasons: murine-derived scFv may limit expansion of CART cells. Repeated antigen exposure leads to T-cell exhaustion. Activation of T cells can cause T-cell senescence and high expression of inhibitive receptors, PD-1, CTLA4, TIGIT,...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Current landscape for chimeric antigen receptor T cells in lymphomas
Purpose of review CART cell therapy has changed the treatment landscape for relapsed/refractory aggressive lymphomas. In this article, we review the CART constructs most studied in lymphoma and their applicability. Recent findings Results of ZUMA-1, JULIET and TRANSCEND trials will be reviewed. Real-world data will also be reviewed. Summary CART cell therapy is evolving and becoming safer. Increased uptake of this modality outside of clinical trials is expected. (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Using minimal (measurable) residual disease assessments to guide decision-making for timing of allogeneic transplantation in acute myeloid leukemia
Purpose of review The current review aims to highlight recent and important developments in the detection and value of minimal (measurable) residual disease (MRD) testing in patients with acute myeloid leukemia (AML) and the impact on the timing of allogeneic hematopoietic cell transplantation. Recent findings The European LeukemiaNet MRD Working Party recently published guidelines to help standardize testing, utilizing flow cytometry and molecular techniques. The timing of MRD assessments, choice of assay and cutoff of for reporting positive results are all important. Patients known to be MRD-positive pretransplantat...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Recent progress in haploidentical transplantation: is this the optimal choice for alternative donor transplantation?
This article is intended to review recent trends and improvements in haploidentical transplantation to understand its current status and future direction. Recent findings The noninferiority of haploidentical donors compared with other donor sources, including HLA-matched related or unrelated donors, has been demonstrated in patients with various hematological diseases. The development of graft-versus-host-disease (GVHD) prophylaxis using posttransplant cyclophosphamide has effectively reduced transplant-related mortality caused by GVHD, graft rejection, and other related complications. Novel GVHD prophylactic methods an...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Allogenic hematopoietic stem cell transplantation in sickle cell disease
Purpose of review Discussing the currently available HSCT options for Hb SS patients highlighting advantages and disadvantages of each modality in the light of recently published data. Recent findings When MSD is available, myeloablative regimen is the preferred approach for otherwise healthy children whereas the nonmyeloablative (NMA) regimen is of choice for adults as well as children with SCD-associated morbidities. Mixed chimerism is common especially with NMA conditioning and is usually enough for cure. Alternative donor HSCT outcomes are progressively improving especially with posttransplant cyclophosphamide for...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Application of stem cell transplantation in autoimmune diseases
Purpose of review Autologous hematopoietic stem cell transplantation (HSCT) is a promising therapeutic modality for severe autoimmune diseases. In this review, we will outline the immunological mechanisms and the clinical evidence and experiences for therapeutic HSCT in autoimmune diseases, with particular focus on systemic sclerosis and multiple sclerosis. Recent findings Approximately 3000 patients with autoimmune diseases worldwide have been treated with HSCT. HSCT in systemic sclerosis has been shown in three randomized controlled trials to be associated with significant long-term event-free survival despite some ...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Is autologous stem cell transplantation still relevant for multiple myeloma?
Purpose of review Autologous stem cell transplantation has been the standard of care in myeloma treatment for many years, but the availability of newer antimyeloma drugs and the emerging data from chimeric antigen receptor (CAR) T-cell clinical studies make us question the relevance of it. The purpose of this review is to go over recent data and to reassess the current status of autologous stem cell transplantation as a standard of care. Recent findings Autologous stem cell transplantation can be safely performed for elderly patients and there is no absolute age limit. Recent data on BEAM (Carmustine, Etoposide, Cytar...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

MICROtransplant to refractory acute myeloid leukemia in Egyptian population
Purpose of review The purpose of this review is to outline Egyptian experience of nonengraftment haploidentical cellular therapy [microtransplantation (MST)] for patients with refractory acute myeloid leukemia. Recent findings The use of granulocyte colony-stimulating factor primed halo-identical MST appears to be a biologically active therapy in patients with refractory acute myeloid leukemia (AML), especially in patients received less than four previous chemotherapy lines, fludarabine-free previous chemotherapy, response naïve and young age patients. Summary Refractory AML is still challenging. MST is promis...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

Current state of nonengrafting donor leukocyte infusion (focus on microtransplantation for acute myeloid leukemia)
Purpose of review Microtransplantation (or micro-stem cell transplantation, MST) is one permutation of alloreactive immunotherapy increasingly studied in clinical trials. It is most commonly applied to patients with myeloid malignancies who are not suitable candidates for allogeneic hematopoietic cell transplantation. This review highlights the past 2 years of work on stem/progenitor cell products in the field of nonengrafting donor leukocyte infusion (NE-DLI), with a focus on applications of MST in acute myeloid leukemia (AML). Recent findings Assessing the utility of MST is hampered by lack of randomized controlled ...
Source: Current Opinion in Hematology - October 4, 2019 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research

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

Antiphospholipid syndrome in pediatric patients
Purpose of review The purpose of this review is to summarize the diagnosis and management of the antiphospholipid syndrome (APS) in children. Recent findings APS is a rare, acquired autoimmune systemic disease that can result in significant morbidity in children related to vascular thrombosis. The diagnosis and management of APS in children can be challenging due to a lack of validated diagnostic criteria and the rarity of the disease. In addition, many healthy children have transient circulating antiphospholipid antibodies without thrombotic complications. Nevertheless, epidemiological studies suggest that APS repres...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

CD36 and ERK5 link dyslipidemia to apoptotic-like platelet procoagulant function
Purpose of review Metabolic diseases, including dyslipidemia, diabetes mellitus, and chronic inflammation are risk factors for clinically significant thrombotic events. Thrombosis in these settings is multifaceted with coordinated mechanisms between platelet activation and the hemostatic pathways. This review focuses on recent advances in platelet procoagulant and apoptotic signaling with emphasis on the pathophysiologic mechanisms induced by platelet CD36 in dyslipidemia, and the key unaddressed questions relating to the field. Recent findings CD36 promotes platelet activation and increases the risk for thrombosis th...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Cancer cell-derived tissue factor-positive extracellular vesicles: biomarkers of thrombosis and survival
Purpose of review Tissue factor (TF) is released from cancer cells and tumors in the form of extracellular vesicles (EVs). This review summarizes our current knowledge of the mechanisms of release of TF-positive EVs (TF+EVs) from cancer cells and the effect of these TF+EVs on cultured endothelial cells. In addition, we will summarize the contribution of TF+EVs to thrombosis in mice, and the association between plasma EVTF activity and venous thrombosis as well as survival of cancer patients. Recent findings The release of TF+EVs from cancer cells is regulated by multiple factors, including hypoxia, epithelial–me...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Does fibrinogen serve the host or the microbe in Staphylococcus infection?
Purpose of review Fibrin(ogen) is a multifunctional clotting protein that not only has critical roles in hemostasis but is also important in inflammatory processes that control bacterial infection. As a provisional extracellular matrix protein, fibrin(ogen) functions as a physical barrier, a scaffold for immune cell migration, or as a spatially-defined cue to drive inflammatory cell activation. These mechanisms contribute to overall host antimicrobial defense against infection. However, numerous bacterial species have evolved mechanisms to manipulate host fibrin(ogen) to promote microbial virulence and survival. Staphylo...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Altered functions of platelets during aging
Purpose of review Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions that also mediate inflammatory responses and neurological diseases. These functions are relevant to disease processes prevalent among older adults and likely influence susceptibility to thrombotic and inflammatory disorders. Recent findings Platelet counts decrease in aged individuals whereas platelet reactivity increases. The platelet transcriptome is altered in aged individuals resulting in altered platelet function and exaggerated in...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

The role of genetics in the pathogenesis and diagnosis of type 1 Von Willebrand disease
Purpose of review Von Willebrand disease (VWD) is a common bleeding disorder, but diagnosis of VWD is challenging, particularly with type 1 VWD. Although most clinicians use specific tests of von Willebrand factor (VWF) activity to classify patients with VWD, genetic testing for VWF defects is another potential method of diagnosis. Recent findings Studies of patients with type 1 VWD report consistently that many, but not all, study participants have VWF gene defects. Certain populations, including those with VWF levels less than 30 IU/dl and those with clearance defects, are more likely to have a VWF sequence varian...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Activated protein C in neuroprotection and malaria
Purpose of review Activated protein C (APC) is a homeostatic coagulation protease with anticoagulant and cytoprotective activities. Focusing on APC's effects in the brain, this review discusses three different scenarios that illustrate how APC functions are intimately affecting the physiology and pathophysiology of the brain. Recent findings Cytoprotective APC therapy holds promise for the treatment of ischemic stroke, and a recently completed trial suggested that cytoprotective-selective 3K3A-APC reduced bleeding in ischemic stroke patients. In contrast, APC's anticoagulant activity contributes to brain bleeding as s...
Source: Current Opinion in Hematology - August 2, 2019 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

Recent advances in inherited platelet disorders
Purpose of review The increasing use of high throughput sequencing and genomic analysis has facilitated the discovery of new causes of inherited platelet disorders. Studies of these disorders and their respective mouse models have been central to understanding their biology, and also in revealing new aspects of platelet function and production. This review covers recent contributions to the identification of genes, proteins and variants associated with inherited platelet defects, and highlights how these studies have provided insights into platelet development and function. Recent findings Novel genes recently implica...
Source: Current Opinion in Hematology - August 2, 2019 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 2, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research

Using genomic data for selecting the treatment of lymphoma patients
Purpose of review Genomic profiling platforms provide unprecedented genetic information of lymphoma biology, yet information has yet to be readily integrated into clinical medicine. This review summarizes the important concepts of utilizing genomics to aide disease management. Recent findings A wide range of clinical grade genetic sequencing platforms are available, therefore the selection of sequencing platform should ideally be based on biological and clinical questions, as well as the strength and weaknesses of individual platform. Different evidence-based guidelines exist to aide clinical judgment; however, few ha...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Role of chromosomal architecture in germinal center B cells and lymphomagenesis
Purpose of review Chromatin organization during interphase is nonrandom, and dictated by a delicate equilibrium between biophysics, transcription factor expression, and topological regulators of the chromatin. Emerging evidence demonstrate a role for chromosomal conformation at different stages of B-cell development. In the present review, we provide an updated picture of the current knowledge regarding how chromosomal conformation regulates the B-cell phenotype and how disruption of this architecture could lead to B-cell lymphoma. Recent findings B-cell development requires proper assembly of a rearranged VDJ locus, ...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Hematopoietic-cell transplantation for lymphoma in the era of genetically engineered cellular therapy: it's not quite time to scrap the old vehicle for the new car
Purpose of review Second-line platinum-based salvage chemotherapy followed by high-dose chemotherapy and autologous hematopoietic-cell transplantation (AHCT) has remained the standard of care (SOC) for relapsed and primary refractory (r/r) diffuse large B-cell lymphoma (DLBCL) for greater than 2 decades. In the postrituximab era, this strategy has yielded disappointing outcomes for r/r patients with curability in less one-quarter of the patients by intention-to-treat. Recent findings Given the Food and Drug Administration (FDA) approval of chimeric antigen receptor (CAR) modified T cells directed against CD19 (CD19 CA...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

The future of cell-free DNA testing to guide therapeutic decisions in B-cell lymphomas
Purpose of review Tissue biopsy is the current gold standard technique for diagnosis and molecular profiling of lymphomas, but it carries several disadvantages in terms of procedural risks (infectious and haemorrhagic complications, anaesthesiologic risks) and analytic aspects (heterogeneity of tumors, low representation of tumor cells in the tissue). Noninvasive genotyping of B-cell lymphomas through circulating tumor DNA (ctDNA) is emerging as a practical tool to monitor the genetics and course of the disease from diagnosis to eventual relapse. This review will explore recent advances in the field of liquid biopsy in ...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Bromodomain and Extra-Terminal domain inhibitors for lymphoid malignancies
Purpose of review Pharmacological inhibition of Bromodomain and Extra-Terminal (BET) domain proteins is a very exciting epigenetic therapeutic modality. Due to the central role of BET proteins in transcription regulation, their inhibition heavily affects lymphoma cells and BET inhibitors show a clear preclinical antitumor activity as single agents and in combination, paired with early reports of clinical activity. Recent findings Relevant data have been recently presented on the mechanism of action of the BET inhibitors, on modalities to improve their activity in lymphomas, and their clinical evaluation. Summary Th...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari M. Melnick Source Type: research

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation
Purpose of review Hematopoietic cell transplantation (HCT) is a life-saving treatment for a variety of hematological and nonhematological disorders. Successful clinical outcomes after transplantation rely on adequate hematopoietic stem cell (HSC) numbers, and the homing and subsequent short-term and long-term engraftment of these cells in the bone marrow. Enhancing the homing capability of HSCs has the potential for high impact on improving HCT and patient survival. Recent findings There are a number of ways to enhance HSC engraftment. Neutralizing negative epigenetic regulation by histone deacetylase 5 (HDAC5) increa...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Hematopoietic stem cells: self-renewal and expansion
Hematopoietic stem cells (HSCs) are a unique population of cells with the remarkable ability to replenish themselves through self-renewal and to give rise to differentiated cell lineages. Though having been discovered more than 50 years ago, and having been widely used in bone marrow transplantation to treat blood disorders including leukemia, expansion of HSCs remains an unmet task, thus affecting its more effective usage in clinical practice. Purpose of review The purpose of this review article is to summarize past efforts in ex-vivo HSC expansion and to compare recent advances in expanding murine and human HSCs by ta...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Normal and leukemic stem cell niche interactions
Purpose of review Normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) interact with the stem cell niche bone marrow in different ways. Understanding the potentially unique microenvironmental regulation of LSCs is key to understanding in-vivo leukemogenic mechanisms and developing novel antileukemic therapies. Recent findings When leukemic cells are engrafted in the stem cell niche, the cellular nature of the niche – including mesenchymal stromal cells – is reprogramed. Altered mesenchymal cells selectively support leukemic cells and reinforce the pro-leukemic environment. As the niche pla...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Defining the functions of adenosine-to-inosine RNA editing through hematology
Purpose of review The direct modification of RNA is now understood to be widespread, evolutionarily conserved and of consequence to cellular and organismal homeostasis. adenosine-to-inosine (A-to-I) RNA editing is one of the most common mammalian RNA modifications. Transcriptome-wide maps of the A-to-I editing exist, yet functions for the majority of editing sites remain opaque. Herein we discuss how hematology has been applied to determine physiological and malignant functions of A-to-I editing. Recent findings Functional studies have established that A-to-I editing and ADAR1, responsible for the majority of editing ...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

p53 involvement in clonal hematopoiesis of indeterminate potential
Purpose of review Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and occurs when a single mutant hematopoietic stem cell (HSC) contributes to a significant clonal proportion of mature blood lineages. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP. This review focuses on mechanisms by which mutant p53 promotes CHIP progression and drives the pathogenesis of hematological malignancies, including myelodysplastic syndromes, and acute myeloid leukemia. Recent findings TP53 was frequently mutated in ind...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Mitochondrial metabolism and the maintenance of hematopoietic stem cell quiescence
Purpose of review Hematopoietic stem cells (HSCs) are characterized by a potent multilineage regenerative capability that is dependent on their quiescence property. In the past few decades, researchers have found many intrinsic and niche-derived factors that can regulate HSCs, whereas how to precisely control HSC behaviors remains elusive. Recently, mitochondrial metabolism has been shown to be involved in the regulation of HSC biology. The purpose of this review is to overview recent advances in the relationship between mitochondrial metabolism and maintenance of HSC quiescence. Recent findings On the basis of fact t...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Growing old in the age of heterogeneity: the perils of shifting clonality
Purpose of review Hematopoietic stem cells (HSC) are functionally heterogeneous in a clone-specific manner. The complexity of that heterogeneous mix of cells is progressively lost with age as a myeloid-dominant hematopoietic system is established. Yet, the function of this diversity, as well as the consequences of its loss, remains unknown. This review will bring together recent advances in HSC diversity and novel insights into myeloid heterogeneity and specification in order to bring focus on how this may affect the ageing individual. Recent findings The ageing haematopoietic system is dominated by a low number of ac...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells
Purpose of review The recent emergence of single-cell technologies has permitted unprecedented insight into the molecular drivers of fate choice in blood stem and progenitor cells. This review gives a broad overview of current efforts to understand the molecular regulators of malignant hematopoietic stem cells (HSCs) at the single-cell level. Recent findings The large-scale adoption of single-cell approaches has allowed extensive description of the transcriptional profiles and functional properties of single HSCs. These techniques are now beginning to be applied to malignant HSCs isolated directly from patients or fro...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Toll-like receptor signaling in hematopoietic stem and progenitor cells
Purpose of review The innate immune system is essential in the protection against microbial infection and facilitating tissue repair mechanisms. During these stresses, the maintenance of innate immune cell numbers through stress-induced or emergency hematopoiesis is key for our survival. One major mechanism to recognize danger signals is through the activation of Toll-like receptors (TLRs) on the surface of hematopoietic cells, including hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC), and nonhematopoietic cells, which recognize pathogen-derived or damaged-induced compounds and can influence the eme...
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - June 7, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Emerging molecular mechanisms of vascular dementia
Purpose of review Microvascular ischemic disease of the brain is a common cause of cognitive impairment and dementia, particularly in the context of preexisting cardiovascular risk factors and aging. This review summarizes our current understanding of the emerging molecular themes that underlie progressive and irreparable vascular disease leading to neuronal tissue injury and dementia. Recent findings Cardiometabolic risk factors including diabetes and hypertension are known to contribute to vascular disease. Currently, the impact of these risk factors on the integrity and function of the brain vasculature has been ta...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

CADASIL: new advances in basic science and clinical perspectives
Purpose of review Recent advances in genetic evaluation improved the identification of several variants in the NOTCH3 gene causing Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Despite improved diagnosis, the disease mechanism remains an elusive target and an increasing number of scientific/clinical groups are investigating CADASIL to better understand it. The purpose of this review is to summarize the current knowledge in CADASIL. Recent findings CADASIL is a genotypically and phenotypically diverse condition involving multiple molecular systems affecting small ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Rapamycin and treatment of venous malformations
Purpose of review The field of vascular anomalies has seen a fundamental change during the past 10 years. The identification of somatic genetic mutations as the explanation of sporadic vascular anomalies opened the doors to study prospectively and a posteriori the causes of various vascular malformations. This was helped by the rapidly evolving genetic techniques including the highly sensitive next generation sequencing. In parallel, knowledge on signaling alterations occurring in vascular endothelial cells because of the various mutations, development of in-vitro and especially the first in-vivo models, gave the possibi...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

A somatic missense mutation in GNAQ causes capillary malformation
Purpose of review Capillary malformations, the most common type of vascular malformation, are caused by a somatic mosaic mutation in GNAQ, which encodes the Gαq subunit of heterotrimeric G-proteins. How the single amino acid change – predicted to activate Gαq – causes capillary malformations is not known but recent advances are helping to unravel the mechanisms. Recent findings The GNAQ R183Q mutation is present not only in endothelial cells isolated from skin and brain capillary malformations but also in brain tissue underlying the capillary malformation, raising questions about the origin of ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

PIK3CA mutations in vascular malformations
Purpose of review Recently, it has been discovered that a subset of vascular malformations, of the lymphatic and venous type, are caused by oncogenic mutations in the PIK3CA gene. Now, efforts have been focused in the understanding of the molecular and cellular consequences of these mutations and the opportunities for novel-targeted therapies for these diseases. Recent findings Here, we review the latest findings in the biology of oncogenic PIK3CA mutations in the pathogenesis of vascular malformations. We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformatio...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Deregulation of Drosha in the pathogenesis of hereditary hemorrhagic telangiectasia
Purpose of review The TGFβ (transforming growth factor β) superfamily – a large group of structurally related and evolutionarily conserved proteins – profoundly shapes and organizes the vasculature during normal development and adult homeostasis. Mutations inactivating several of its ligands, receptors, or signal transducers set off hereditary hemorrhagic telangiectasia (HHT), a disorder that causes capillary networks to form incorrectly. Drosha, an essential microRNA-processing enzyme, also interfaces with TGFβ signal transducers, but its involvement in vascular conditions had not been tested ...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

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