Update in clinical and mouse microbiota research in allogeneic haematopoietic cell transplantation
Purpose of review
The intestinal microbiota plays a critical role in intestinal homeostasis and immune regulation and has been recognized as a predictor of clinical outcome in patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT) and specifically a determinant of the severity of graft-versus-host disease (GVHD) in mouse models. As GVHD is the most important cause of nonrelapse mortality (NRM) after allo-HCT, understanding the mechanisms by which modifying the microbiota may prevent or decrease the severity of GVHD would represent an important advance.
Recent findings
Microbiota injury was obser...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Pavan Reddy Source Type: research
Immunometabolism in haematopoietic stem cell transplantation and adoptive cellular therapies
Purpose of review
Controlling T cell activity through metabolic manipulation has become a prominent feature in immunology and practitioners of both adoptive cellular therapy (ACT) and haematopoietic stem cell transplantation (HSCT) have utilized metabolic interventions to control T cell function. This review will survey recent metabolic research efforts in HSCT and ACT to paint a broad picture of immunometabolism and highlight advances in each area.
Recent findings
In HSCT, recent publications have focused on modifying reactive oxygen species, sirtuin signalling or the NAD salvage pathway within alloreactive T cells a...
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Pavan Reddy Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - October 3, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research
The interaction between the complement system and hemostatic factors
Purpose of review
To discuss the crosstalk between the complement system and hemostatic factors (coagulation cascade, platelet, endothelium, and Von Willebrand Factor), and the consequences of this interaction under physiologic and pathologic conditions.
Recent findings
The complement and coagulation systems are comprised of serine proteases and are genetically related. In addition to the common ancestral genes, the complement system and hemostasis interact directly, through protein–protein interactions, and indirectly, on the surface of platelets and endothelial cells. The close interaction between the complement s...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Updates in diagnosis of the inherited platelet disorders
Purpose of review
To provide a comprehensive update on the current available methodologies and techniques for diagnosis of inherited platelet disorders (IPD).
Recent findings
The contributions of many groups have resulted in the significant progress in the molecular diagnosis of IPD including the identification of many genes responsible for the various phenotypes. The widespread use and availability of next-generation sequencing has brought to the forefront ethical challenges associated with nontargeted sequencing as well as provided us with novel variants to functionally validate. These requirements have driven the d...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Venous thromboembolism in the hormonal milieu
Purpose of review
Hormonal therapy is administered for multiple indications including contraception, alleviation of menopausal symptoms, hypogonadism, and more recently, gender-affirming care. Data suggest varying degrees of increased risk for venous thromboembolism (VTE).
Recent findings
While oral progestin only methods do not appear to increase the risk of VTE, an association was seen with injection progestin contraception. Combined oral contraception with low-dose ethinyl estradiol and most types of progestin increased the risk of VTE compared with levonorgestrel-containing oral therapies. While transdermal hormon...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Insights into ADAMTS13 structure: impact on thrombotic thrombocytopenic purpura diagnosis and management
Purpose of review
Fundamental knowledge on the role of a disintegrin and metalloprotease with thrombospondin type one repeats, member 13 (ADAMTS13) has been crucial to better understand the pathophysiology of the rare and life-threatening disease thrombotic thrombocytopenic purpura (TTP).
Recent findings
ADAMTS13 works through a molecular zipper mechanism to proteolyze its substrate von Willebrand factor (VWF). Recent insights into the structure and function of ADAMTS13 led to the identification of an allosteric activation mechanism. Therefore, ADAMTS13 is roughly folded in two in which the N-terminal spacer (S) domai...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
The rebirth of the contact pathway: a new therapeutic target
Purpose of review
Anticoagulation with vitamin-K antagonists or direct oral anticoagulants is associated with a significant risk of bleeding. There is a major effort underway to develop antithrombotic drugs that have a smaller impact on hemostasis. The plasma contact proteins factor XI (FXI) and factor XII (FXII) have drawn considerable interest because they contribute to thrombosis but have limited roles in hemostasis. Here, we discuss results of preclinical and clinical trials supporting the hypothesis that the contact system contributes to thromboembolic disease.
Recent findings
Numerous compounds targeting FXI or ...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Molecular and functional characteristics of megakaryocytes and platelets in aging
Purpose of review
Advances in medical care and preventive measures have contributed to increasing life expectancy. Therefore, it is critical to expand our understanding of the physiological and pathophysiological adaptations of the hematological system in aging. We highlight and review the findings from recent investigations aimed at understanding the effects of aging on megakaryocytes and platelets.
Recent findings
Biochemical and transcriptomic studies of megakaryocytes and platelets from older humans and mice have advanced our understanding of the molecular and functional characteristics of megakaryocytes and plate...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Nonsevere hemophilia A: often overlooked, but not forgotten
Purpose of review
Nonsevere hemophilia A (NSHA) patients have received relatively little clinical and research attention as compared with their severe counterparts. There is increasing recognition that despite their milder bleeding phenotype, the management of NSHA can be a challenge, with most management decisions largely inferred from severe hemophilia A data. This review focuses on some of the more recent developments in the field of NSHA.
Recent findings
Epidemiologic studies suggest that NSHA remain under-recognized and under-diagnosed globally. As the NSHA population ages, they are susceptible to age-related com...
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 4, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research
Germline mutations: many roles in leukemogenesis
Purpose of review
The purpose of this review is to summarize the current understanding of germline mutations as they contribute to leukemia development and progression. We also discuss how these new insights may help improve clinical management of germline mutations associated with leukemia.
Recent findings
Germline mutations may represent important initial mutations in the development of leukemia where interaction with somatic mutations provide further hits in leukemic progression. In addition, germline mutations may also contribute to leukemogenesis by impacting bone marrow stem-cell microenvironment and immune cell...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Regulation of stress-induced hematopoiesis
Purpose of review
The hematopoietic compartment is tasked with the establishment and maintenance of the entire blood program in steady-state and in response to stress. Key to this process are hematopoietic stem cells (HSCs), which possess the unique ability to self-renew and differentiate to replenish blood cells throughout an organism's lifetime. Though tightly regulated, the hematopoietic system is vulnerable to both intrinsic and extrinsic factors that influence hematopoietic stem and progenitor cell (HSPC) fate. Here, we review recent advances in our understanding of hematopoietic regulation under stress conditions s...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
In vivo and ex vivo haematopoietic stem cell expansion
Purpose of review
Haematopoietic stem cells (HSCs) are characterized by two key features: self-renewal ability and multilineage differentiation potential. Through these cellular activities, HSCs sustain blood and immune system homeostasis throughout life and can also reconstitute the entire haematopoietic system within a bone marrow ablated recipient. This approach of HSC transplantation is used clinically as a curative treatment option for numerous haematological diseases, both malignant and nonmalignant.
Recent findings
Elucidation of the mechanism of HSC expansion represents a major focus within haematology. Here, ...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
Hematopoietic regeneration under the spell of epigenetic-epitranscriptomic factors and transposable elements
Purpose of review
Since the discovery of master transcription factors that regulate hematopoietic regeneration following different stressors, many more layers of regulation have been discovered. The purpose of this review is to outline the recent discoveries of epigenetic and epitranscriptomic control of hematopoietic regeneration and highlight the novel involvement of transposable elements in this process.
Recent findings
Over the past 2 years, we have gained additional knowledge in the role of epigenetic regulators in hematopoietic regeneration. Histone modifiers, like SETD1A, JARID2, KDM6B, and classic DNA methylat...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research
