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 plays an 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
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
