Still a burning question: the interplay between inflammation and fibrosis in myeloproliferative neoplasms
Purpose of review Bone marrow fibrosis is the progressive replacement of blood-forming cells by reticulin fibres, caused by the acquisition of somatic mutations in hematopoietic stem cells. The molecular and cellular mechanisms that drive the progression of bone marrow fibrosis remain unknown, yet chronic inflammation appears to be a conserved feature in most patients suffering from myeloproliferative neoplasms. Recent findings Here, we review recent literature pertaining to the role of inflammation in driving bone marrow fibrosis, and its effect on the various hematopoietic and nonhematopoietic cell populations...
Source: Current Opinion in Hematology - August 6, 2021 Category: Hematology Tags: CLONAL HEMATOPOIESIS (CHIP) AND MYELODYSPLASIA (MDS): Edited by Borhane Guezguez Source Type: research

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

The Nlrp3 inflammasome – the evolving story of its positive and negative effects on hematopoiesis
Purpose of review Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the Nlrp3 inflammasome, which is an intracellular innate immunity pattern recognition receptor and sensor of changes in the hematopoietic microenvironment, and focus on its role in hematopoieisis. Recent findings Hematopoietic stem progenitor cells (HSPCs) are exposed to several external mediators of innate immunity. Moreover, since hemato/lymphopoietic cells develop from...
Source: Current Opinion in Hematology - June 11, 2021 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L Capitano Source Type: research

Cellular components of the hematopoietic niche and their regulation of hematopoietic stem cell function
Purpose of review Development and functions of hematopoietic stem cells (HSC) are regulated by multiple cellular components of the hematopoietic niche. Here we review the recent advances in studying the role of three such components -- osteoblasts, osteomacs, and megakaryocytes and how they interact with each other in the hematopoietic niche to regulate HSC. Recent findings Recent advances in transgenic mice models, scRNA-seq, transcriptome profile, proteomics, and live animal imaging have revealed the location of HSC within the bone and signaling molecules required for the maintenance of the niche. Interaction ...
Source: Current Opinion in Hematology - June 11, 2021 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L Capitano Source Type: research

Consequences of coronavirus infections for primitive and mature hematopoietic cells: new insights and why it matters
Purpose of review In recent history there have been three outbreaks of betacoronavirus infections in humans, with the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; causing Coronavirus disease 2019 [COVID-19]) outbreak leading to over two million deaths, with a rapidly rising death toll. Much remains unknown about host cells and tissues affected by coronavirus infections, including the hematopoietic system. Here, we discuss the recent findings examining effects that coronavirus infection or exposure has on hematopoietic cells and the clinical implications for these effects. Recent findings ...
Source: Current Opinion in Hematology - June 11, 2021 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 11, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Single-cell RNA sequencing to study vascular diversity and function
Purpose of review Single-cell RNA sequencing (scRNA-seq) can capture the transcriptional profile of thousands of individual cells concurrently from complex tissues and with remarkable resolution. Either with the goal of seeking information about distinct cell subtypes or responses to a stimulus, the approach has provided robust information and promoted impressive advances in cardiovascular research. The goal of this review is to highlight strategies and approaches to leverage this technology and bypass potential caveats related to evaluation of the vascular cells. Recent findings As the most recent technological...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Enhancing cardiovascular research with whole-organ imaging
Purpose of review There have been tremendous advances in the tools available for surveying blood vessels within whole organs and tissues. Here, we summarize some of the recent developments in methods for immunolabeling and imaging whole organs and provide a protocol optimized for the heart. Recent findings Multiple protocols have been established for chemically clearing large organs and variations are compatible with cell type-specific labeling. Heart tissue can be successfully cleared to reveal the three-dimensional structure of the entire coronary vasculature in neonatal and adult mice. Obtaining vascular reco...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Methods to quantify endothelial cell front-rear polarity in vivo and in vitro
We present a literature-based review of the methods available to study EC polarity. Further refinement of quantitative methods to analyse EC axial polarity using deep learning-based computational tools will generate new understanding on the aetiology of vascular malformations. (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

A zebrafish toolbox for biomechanical signaling in cardiovascular development and disease
Purpose of review The zebrafish embryo has emerged as a powerful model organism to investigate the mechanisms by which biophysical forces regulate vascular and cardiac cell biology during development and disease. A versatile arsenal of methods and tools is available to manipulate and analyze biomechanical signaling. This review aims to provide an overview of the experimental strategies and tools that have been utilized to study biomechanical signaling in cardiovascular developmental processes and different vascular disease models in the zebrafish embryo. Within the scope of this review, we focus on work published durin...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Intricacies of conditional genetics in vascular biology
Purpose of review Conditional or inducible recombinase-based genetics is still the gold standard to analyse gene function, given its high specificity, temporal control, limited toxicity and the many available genetic tools. However, it is based on methods that have inherent limitations and shortcomings. The purpose of this review is to summarize and contrast the different available methods used to perform conditional gene function analysis to better inform the community about their particularities and the need to use better methods. Recent findings As any other biomedical field, the vascular biology field has mo...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Mouse models of vascular development and disease
Purpose of review The use of genetic models has facilitated the study of the origins and mechanisms of vascular disease. Mouse models have been developed to specifically target endothelial cell populations, with the goal of pinpointing when and where causative mutations wreck their devastating effects. Together, these approaches have propelled the development of therapies by providing an in-vivo platform to evaluate diagnoses and treatment options. This review summarizes the most widely used mouse models that have facilitated the study of vascular disease, with a focus on mouse models of vascular malformations and the ...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Editorial: New technological developments and their impact in vascular research
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Ineffective erythropoiesis in sickle cell disease: new insights and future implications
Purpose of review Sickle cell disease (SCD) is a hemolytic anemia caused by a point mutation in the β globin gene leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions driving red cell sickling. Circulating red cells have been extensively characterized in SCD, as their destruction and removal from peripheral blood are the major contributors to anemia. However, few reports showed cellular abnormalities during erythropoiesis in SCD, suggesting that anemia could also be influenced by defects of central origin. Recent findings El Hoss et al. demonstrated ineffective...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Heterogeneity of fetal hemoglobin production in adult red blood cells
Purpose of review Small amounts of fetal hemoglobin can be expressed in a subset of adult red blood cells called F-cells. This review examines the potential mechanisms and clinical implications of the heterogeneity of fetal hemoglobin expression. Recent findings Although the heterocellular nature of fetal hemoglobin expression in adult red blood cells has been noted for over 70 years, the molecular basis of this phenomenon has been unclear. Recent discoveries of novel regulators of fetal hemoglobin as well as technological advances have shed new light on these cells. Summary Fetal hemoglobin reactivation ...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Erythroid cells and malaria parasites: it's a match!
Purpose of review The current review outlines recent discoveries on the infection of erythroid cells by Plasmodium parasites, focusing on the molecular interactions governing the tropism of parasites for their host cell and the implications of this tropism for parasite biology and erythroid cell maturation. Recent findings Although most studies about the interactions of Plasmodium parasites and their host cell focused on the deadliest human malaria parasite, Plasmodium falciparum, and the erythrocyte, there is increasing evidence that several Plasmodium species, including P. falciparum, also develop within eryth...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Proteomic/transcriptomic analysis of erythropoiesis
Purpose of review Erythropoiesis is a hierarchical process by which hematopoietic stem cells give rise to red blood cells through gradual cell fate restriction and maturation. Deciphering this process requires the establishment of dynamic gene regulatory networks (GRNs) that predict the response of hematopoietic cells to signals from the environment. Although GRNs have historically been derived from transcriptomic data, recent proteomic studies have revealed a major role for posttranscriptional mechanisms in regulating gene expression during erythropoiesis. These new findings highlight the need to integrate proteomic d...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology
Purpose of review This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies. Recent findings Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of these biophysical and rheological properties in normoxia or physiological hypoxia in a clinically meaningful way. There are emerging targe...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

‘Enhancing’ red cell fate through epigenetic mechanisms
Purpose of review Transcription of erythroid-specific genes is regulated by the three-dimensional (3D) structure and composition of chromatin, which dynamically changes during erythroid differentiation. Chromatin organization and dynamics are regulated by several epigenetic mechanisms involving DNA (de-)methylation, posttranslational modifications (PTMs) of histones, chromatin-associated structural proteins, and higher-order structural changes and interactions. This review addresses examples of recent developments in several areas delineating the interface of chromatin regulation and erythroid-specific lineage transcri...
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 3, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Novel developments in chronic myeloid leukaemia
Purpose of review Despite unprecedented challenges during the preceding year, there have been a wide range of significant advances in the field of chronic myeloid leukaemia. In this review article we highlight papers reporting on some of the most important developments over the last year, both with regards to the clinical management of patients with chronic myeloid leukaemia, as well as studies that help to increase our understanding of the pathophysiology of the disease. We have performed a PubMed search to identify important papers and abstracts listed over the last year and have included additional papers published ...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission
Purpose of review Maintenance therapy for acute myeloid leukemia (AML) has been studied for decades with mixed results. However, the application of modern agents has renewed interest and the recent data from randomized trials has provided evidence for the use of maintenance therapy in certain populations of AML patients. Recent findings Unselected patients are unlikely to benefit from maintenance therapy as has been previously and consistently demonstrated. The increasing availability of newer and targeted agents like oral hypomethylating agents, protein modifiers, as well as FLT3, IDH1/2 BCL-2 and immune checkp...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Prognostic mutation constellations in acute myeloid leukaemia and myelodysplastic syndrome
Purpose of review In the past decade, numerous studies analysing the genome and transcriptome of large cohorts of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients have substantially improved our knowledge of the genetic landscape of these diseases with the identification of heterogeneous constellations of germline and somatic mutations with prognostic and therapeutic relevance. However, inclusion of integrated genetic data into classification schema is still far from a reality. The purpose of this review is to summarize recent insights into the prevalence, pathogenic role, clonal architecture, ...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Clonal hematopoiesis in hematopoietic stem cell transplantation
Purpose of review Clonal hematopoiesis (CH) is characterized by the acquisition of somatic mutations and subsequent expansion of mutated hematopoietic stem and progenitor cell (HSPC) clones without clinical evidence for a hematologic neoplasm. The prevalence of CH continuously increases with age reaching double-digit percentages in individuals>60 years. CH is associated with an increased risk for hematologic neoplasms and cardiovascular disease. We will review recent efforts to investigate how CH influences patient outcomes in hematopoietic stem cell transplantation – both autologous (ASCT) and allogeneic (all...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Germline mutations in MDS/AML predisposition disorders
Purpose of review Recognition of hereditary hematopoietic malignancies impacts patient management as well as health surveillance strategies for the patient and relatives who share the causative DNA variant. In this review, barriers to the diagnosis and management of patients are outlined. Recent findings Increasingly, individuals are being recognized as having germline predisposition to hematopoietic malignancies. Clinical testing for these syndromes is difficult for most clinicians given the need to send true germline samples and the lack of standardization in the field with regard to which genes are covered an...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

The N6-methyladenosine RNA modification in acute myeloid leukemia
Purpose of review In recent years, the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs). In this review we summarise the recent findings in the field of epitranscriptomics related to m6A and its relevance in AML. Recent findings Recent studies have focused on the role of m6A regulators in the development of AML and their potential as translational targets. The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-co...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Therapeutic approaches targeting splicing factor mutations in myelodysplastic syndromes and acute myeloid leukemia
Purpose of review Mutations in components of the spliceosome are the most common acquired lesions in myelodysplastic syndromes (MDS) and are frequently identified in other myeloid malignancies with a high rate of progression to acute myeloid leukemia (AML) including chronic myelomonocytic leukemia and primary myelofibrosis. The only curative option for these disorders remains allogeneic stem-cell transplantation, which is associated with high morbidity and mortality in these patients. The purpose of this review is to highlight the recent therapeutic developments and strategies being pursued for clinical benefit in spli...
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Editorial: Do not lose focus on myeloid biology in the era of COVID-19
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: MYELOID DISEASE: Edited by Stephanie Halene and Thomas Prebet Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2021 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Genetic heterogeneity and clonal evolution in acute myeloid leukemia
Purpose of review Clonal heterogeneity is a significant obstacle to successful treatment of patients with acute myeloid leukemia (AML). Here, we review new advances in the understanding of genetic heterogeneity in AML using single-cell DNA-sequencing technology. Recent findings New genomics and immunologic discovery tools have provided single-cell resolution maps of the clonal architecture of AML. The use of these technologies reveals the mutational landscape of AML at diagnosis, during treatment, and at relapse has an enormous degree of clonal complexity and diversity that is poised to adapt and evolve under en...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Human hematopoiesis: aging and leukemogenic risk
Purpose of review Our understanding of the effects of aging on human hematopoiesis has advanced significantly in recent years, yet the full ramifications of these findings are not fully understood. This review summarizes these findings and discusses their implication as they relate to malignant hematopoiesis. Recent findings With human aging there is an impaired immune response, loss of hematopoietic stem cell (HSC) function, increase in clonal hematopoiesis, and higher frequency of myeloid malignancies. Although murine models have implicated abnormalities in DNA damage repair, autophagy, metabolism, and epigene...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Studying clonal evolution of myeloid malignancies using induced pluripotent stem cells
Purpose of review Myeloid malignancies comprise a spectrum of genetically heterogeneous disorders marked by the stepwise acquisition of somatic mutations and clonal evolution. The blood and bone marrow of patients typically consists of a mix of different clones and subclones along the path of clonal evolution that cannot be deconvoluted with most current approaches. Here, we review the application of induced pluripotent stem cell (iPSC) technology to the study of the clonal architecture and clonal evolution of these diseases, focusing on myelodysplastic syndromes and acute myeloid leukemia. Recent findings Repro...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Blood in the water: recent uses of zebrafish to study myeloid biology
Purpose of review Myeloid cells contribute to immune response to infection and tissue regeneration after injury as well as to the developmental induction of the hematopoietic system overall. Here we review recent uses of zebrafish to advance the study of myeloid biology in development and disease. Recent findings Recent studies have made use of advanced imaging and genetic strategies and have highlighted key concepts in myeloid cell behavior. These include immune-cell cross-talk and subpopulation response in infection and regeneration, and tightly regulated inflammatory and tissue remodeling behaviors in develop...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Structural organization of the bone marrow and its role in hematopoiesis
Purpose of review The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of hematopoietic stem cells (HSC), multipotent progenitors (MPP), and lineage committed progenitors to produce the large number of blood cells required to sustain life. The bone marrow is notoriously difficult to image; because of this the anatomy of blood cell production -- and how local signals spatially organize hematopoiesis -- are not well defined. Here we review our current understanding of the spatial organization of the mouse bone marrow w...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Current understanding of human megakaryocytic-erythroid progenitors and their fate determinants
Purpose of review This review focuses on our current understanding of fate decisions in bipotent megakaryocyte-erythroid progenitors (MEPs). Although extensive research has been carried out over decades, our understanding of how MEP commit to the erythroid versus megakaryocyte fate remains unclear. Recent findings We discuss the isolation of primary human MEP, and focus on gene expression patterns, epigenetics, transcription factors and extrinsic factors that have been implicated in MEP fate determination. We conclude with an overview of the open debates in the field of MEP biology. Summary Understanding ...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research

Systems analysis of hematopoiesis using single-cell lineage tracing
Purpose of review In the last few decades, revolutionary advances in next-generation sequencing have led to single-cell lineage tracing technologies that now enable researchers to identify and quantify hematopoietic cell behavior with unprecedented detail. Combined readouts of cell lineage and cell state from the same cell mitigate the need to prospectively isolate populations of interest, and allow a system-level understanding of dynamic developmental processes. We will discuss the advantages and shortcomings of these technologies, the intriguing discoveries that stemmed from lineage tracing hematopoiesis at the singl...
Source: Current Opinion in Hematology - December 8, 2020 Category: Hematology Tags: MYELOID BIOLOGY: Edited by H. Leighton Grimes Source Type: research