Next generation epigenetic modulators to target myeloid neoplasms
Purpose of review
Comprehensive sequencing studies aimed at determining the genetic landscape of myeloid neoplasms have identified epigenetic regulators to be among the most commonly mutated genes. Detailed studies have also revealed a number of epigenetic vulnerabilities. The purpose of this review is to outline these vulnerabilities and to discuss the new generation of drugs that exploit them.
Recent findings
In addition to deoxyribonucleic acid-methylation, novel epigenetic dependencies have recently been discovered in various myeloid neoplasms and many of them can be targeted pharmacologically. These include...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: CLONAL HEMATOPOIESIS (CHIP) AND MYELODYSPLASIA (MDS): Edited by Borhane Guezguez Source Type: research
Clonal hematopoiesis and myeloid malignancies: clonal dynamics and clinical implications
Purpose of review
Clinical and experimental studies have uncovered relevant clinical implications of clonal hematopoiesis. However, the true magnitude of this process, clonal dynamics over time and mechanisms of progression into overt malignancy remain to be largely elucidated. In this article, the consequences of clonal hematopoiesis, its significance in the context of cytopenia, and its implications in the clinical management of patients with myeloid malignancies are reviewed and discussed.
Recent findings
Clonal hematopoiesis has been associated with higher risk of hematologic cancers, as well as of death fro...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: CLONAL HEMATOPOIESIS (CHIP) AND MYELODYSPLASIA (MDS): Edited by Borhane Guezguez Source Type: research
Editorial: the new age of clinical research in clonal hematopoiesis and myeloid malignancies
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: CLONAL HEMATOPOIESIS (CHIP) AND MYELODYSPLASIA (MDS): Edited by Borhane Guezguez Source Type: research
Protein S: function, regulation, and clinical perspectives
Purpose of review
Protein S (PS) is an essential natural anticoagulant. PS deficiency is a major contributor to acquired hypercoagulability. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals. Yet, despite its importance in hemostasis, PS is the least understood anticoagulant. Even after 40 years since PS was first described, we are still uncovering information about how PS functions. The purpose of this review is to highlight recent findings that advance our understanding of the functions of PS and explain hypercoagulability caused by severe PS defic...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Significance and management of isolated distal deep vein thrombosis
Purpose of review
Management of isolated distal deep vein thrombosis (IDDVT) remains controversial. We summarize recent studies regarding the natural history of IDDVT as well as pertinent therapeutic trials. We also provide our management approach.
Recent findings
IDDVT is more commonly associated with transient risk factors and less often associated with permanent, unmodifiable risk factors than proximal DVT. IDDVT has a significantly lower risk of proximal extension and recurrence than proximal DVT. Cancer-associated IDDVT has a similar natural history to cancer-associated proximal DVT, with substantially less...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Prothrombotic state associated with preeclampsia
Purpose of review
Preeclampsia is a common complication of pregnancy and contributes significantly to maternal and fetal morbidity and mortality. A protective hypercoagulable state is often developed during late pregnancy and can evolve into a prothrombotic state in patients with preeclampsia. The underlying mechanism of this prothrombotic transition remains poorly understood. We discuss recent progress in understanding the pathophysiology of preeclampsia and associated prothrombotic state.
Recent findings
The hypercoagulable state developed during pregnancy is initiated by placental factors and progresses into ...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Regulation and importance of factor VIII levels in hemophilia A carriers
Purpose of review
To summarize the recent literature related to female hemophilia A carriers with respect to prevalence in the population, the impact of baseline factor VIII levels and other influences on bleeding phenotype, and clinical management needs.
Recent findings
Many female hemophilia A carriers are at risk for abnormal bleeding, yet they are underrecognized by healthcare providers and their bleeding symptoms are underreported. Low FVIII levels are consistently associated with clinically significant bleeding and correlate well with skewed X chromosome inactivation (XCI). Most interestingly, bleeding ten...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Modeling genetic platelet disorders with human pluripotent stem cells: mega-progress but wanting more on our plate(let)
Purpose of review
Megakaryocytes are rare hematopoietic cells that play an instrumental role in hemostasis, and other important biological processes such as immunity and wound healing. With the advent of cell reprogramming technologies and advances in differentiation protocols, it is now possible to obtain megakaryocytes from any pluripotent stem cell (PSC) via hematopoietic induction. Here, we review recent advances in PSC-derived megakaryocyte (iMK) technology, focusing on platform validation, disease modeling and current limitations.
Recent findings
A comprehensive study confirmed that iMK can recapitulate ma...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Brothers in arms: platelets and neutrophils in ischemic stroke
Purpose of review
In this review, we will describe how the combined ability of platelets and neutrophils to interact with each other drives ischemic stroke brain injury.
Recent findings
Neutrophils are one of the first cells to respond during ischemic stroke. Although animals stroke models have indicated targeting neutrophils improves outcomes, clinical trials have failed to yield successful strategies. Platelets play a critical role in recruiting neutrophils to sites of injury by acting as a bridge to the injured endothelium. After initial platelet adhesion, neutrophils can rapidly bind platelets through P-sele...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Secondary stroke prevention in patients with patent foramen ovale
Purpose of review
Although a patent foramen ovale (PFO) is an established risk factor for cryptogenic ischemic stroke, strategies for secondary prevention remain controversial. Increasing evidence over the past decade from well designed clinical trials supports transcatheter PFO closure for selected patients whose stroke was likely attributable to the PFO. However, patient selection using imaging findings, clinical scoring systems, and in some cases, thrombophilia testing, is crucial for determining patients most likely to benefit from closure, anticoagulation, or antiplatelet therapy.
Recent findings
Recent stu...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Thrombosis in myeloproliferative neoplasms: update in pathophysiology
Purpose of review
This review summarizes high-impact research in myeloproliferative neoplasms (MPN) from the last 18 months, with a particular focus on basic science findings.
Recent findings
A pseudo-hypoxia state with stabilization of hypoxia-inducible factor (HIFα exists that is central to cell growth, cell renewal, inflammation, and thrombotic potential in MPN hematopoietic cells.
Summary
HIFα and inflammatory pathways are new therapeutic targets in MPN, with the potential to ameliorate thrombotic risk and perhaps eradicate mutant progenitor cells. (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Paul F. Bray Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Splicing regulation in hematopoiesis
Purpose of review
Splicing mutations are among the most recurrent genetic perturbations in hematological malignancies, highlighting an important impact of splicing regulation in hematopoietic development. However, compared to our understanding of splicing factor mutations in hematological malignancies, studies of splicing components and alternative splicing in normal hematopoiesis have been less well investigated. Here, we outline the most recent findings on splicing regulation in normal hematopoiesis and discuss the important questions in the field.
Recent findings
Recent studies have highlighted the critical r...
Source: Current Opinion in Hematology - June 11, 2021 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L Capitano Source Type: research
Deciphering transcriptional and functional heterogeneity in hematopoiesis with single-cell genomics
Purpose of review
Single-cell genomic approaches have uncovered cell fate biases and heterogeneity within hematopoietic subpopulations. However, standard single-cell transcriptomics suffers from high sampling noise, which particularly skews the distribution of lowly expressed genes, such as transcription factors (TFs). This might preclude the identification of rare transcripts that define cell identity and demarcate cell fate biases. Moreover, these studies need to go hand in hand with relevant functional assays to ensure that observed gene expression changes represent biologically meaningful alterations.
Recent fin...
Source: Current Opinion in Hematology - June 11, 2021 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L Capitano Source Type: research
Symmetric and asymmetric activation of hematopoietic stem cells
Purpose of review
Hematopoietic stem cells (HSCs) are in an inactive quiescent state for most of their life. To replenish the blood system in homeostasis and after injury, they activate and divide. HSC daughter cells must then decide whether to return to quiescence and metabolic inactivity or to activate further to proliferate and differentiate and replenish lost blood cells. Although the regulation of HSC activation is not well understood, recent discoveries shed new light on involved mechanisms including asymmetric cell division (ACD).
Recent findings
HSC metabolism has emerged as a regulator of cell fates. Re...
Source: Current Opinion in Hematology - June 11, 2021 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L Capitano Source Type: research
