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 compleme...
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

Hematopoietic stem cell regulation by the proteostasis network
Purpose of review Protein homeostasis (proteostasis) is maintained by an integrated network of physiological mechanisms and stress response pathways that regulate the content and quality of the proteome. Maintenance of cellular proteostasis is key to ensuring normal development, resistance to environmental stress, coping with infection, and promoting healthy aging and lifespan. Recent studies have revealed that several proteostasis mechanisms can function in a cell-type-specific manner within hematopoietic stem cells (HSCs). Here, we review recent studies demonstrating that the proteostasis network functions uniquely in ...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Plant homeodomain finger protein 6 in the regulation of normal and malignant hematopoiesis
Purpose of review Even though an increasing amount of sequencing data on the leukemia genome has highlighted a tumor-suppressive function for plant homeodomain finger protein 6 (PHF6), its role in the hematopoietic system remained elusive until recently. The purpose of this review is to describe the role of PHF6 in normal hematopoiesis and leukemogenesis based on recent findings from knockout mouse models. Recent findings In a mouse model, the loss of Phf6 enhanced the bone marrow repopulating capacity of hematopoietic stem cells (HSCs) during serial transplantations without transforming hematopoietic cells, whereas d...
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 differentiation of adult hematopoietic stem cells from a single-cell point of view
Purpose of review Although hematopoietic stem cell (HSC) function has long been studied by transplantation assays, this does not reflect what HSCs actually do in their native context. Here, we review recent technologic advances that facilitate the study of HSCs in their native context focusing on inducible HSC-specific lineage tracing and inference of hematopoietic trajectories through single-cell RNA sequencing (scRNA-Seq). Recent findings Lineage tracing of HSCs at the population level using multiple systems has suggested that HSCs make a major contribution to steady-state hematopoiesis. Although several genetic sys...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Single-cell fate decisions of bipotential hematopoietic progenitors
Purpose of review In hematopoiesis, rapid cell fate decisions are necessary for timely responses to environmental stimuli resulting in the production of diverse types of blood cells. Early studies have led to a hierarchical, tree-like view of hematopoiesis with hematopoietic stem cells residing at the apex and serially branching out to give rise to bipotential progenitors with increasingly restricted lineage potential. Recent single-cell studies have challenged some aspects of the classical model of hematopoiesis. Here, we review the latest articles on cell fate decision in hematopoietic progenitors, highlighting single-...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

Protection of hematopoietic stem cells from stress-induced exhaustion and aging
Purpose of review Hematopoietic stem cells (HSCs) are defined by their ability to self-renew and differentiate to replenish all blood lineages throughout adult life. Under homeostasis, the majority of HSCs are quiescent, and few stem cells are cycling to sustain hematopoiesis. However, HSCs can be induced to proliferate and differentiate in response to stress signals produced during infection, inflammation, chemotherapy, radiation, bone marrow transplantation, and aging. Recent evidence suggests that acute and chronic stress impact the number and function of HSCs including their ability to repopulate and produce mature c...
Source: Current Opinion in Hematology - June 6, 2020 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

An expanded role for dipeptidyl peptidase 4 in cell regulation
Purpose of review Dipeptidyl peptidase 4 (DPP4) is a serine protease with diverse regulatory functions in healthy and diseased cells. Much remains unknown about the mechanisms and targets of DPP4. Here we discuss new studies exploring DPP4-mediated cellular regulation, provide an updated list of potential targets of DPP4, and discuss clinical implications of each. Recent findings Recent studies have sought enhanced efficacy of targeting DPP4's role in regulating hematopoietic stem and progenitor cells for improved clinical application. Further studies have identified DPP4 functions in different cellular compartments a...
Source: Current Opinion in Hematology - June 6, 2020 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 6, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis
Purpose of review Since the first discovery of Angiopoetin-like 4 (ANGPTL4) in 2000, the involvement of ANGPTL4 in different aspects of lipid metabolism and vascular biology has emerged as an important research field. In this review, we summarize the fundamental roles of ANGPTL4 in regulating metabolic and nonmetabolic functions and their implication in lipid metabolism and with several aspects of vascular function and dysfunction. Recent findings ANGPTL4 is a secreted glycoprotein with a physiological role in lipid metabolism and a predominant expression in adipose tissue and liver. ANGPTL4 inhibits the activity of l...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Podosomes in endothelial cell--microenvironment interactions
Purpose of review The discovery of podosomes in endothelial cells during the process of angiogenesis in vivo opens a new era in vascular biology. Podosomes are actin-based microdomains located at the plasma membrane that have been extensively described but in vitro and in other cells. This review focuses on podosomes in endothelial cells and aims to rise hypotheses about when and how these structures mediate cell--microenvironment interactions. Recent findings A wealth of new information regarding podosome organization and functioning has been collected in simple 2D models. Characterization of their modular architectu...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Vascular elastic fiber heterogeneity in health and disease
Purpose of review Elastin has historically been described as an amorphous protein that functions to provide recoil to tissues that stretch. However, evidence is growing that elastin's role may not be limited to biomechanics. In this minireview, we will summarize current knowledge regarding vascular elastic fibers, focusing on structural differences along the arterial tree and how those differences may influence the behavior of affiliated cells. Recent findings Regional heterogeneity, including differences in elastic lamellar number, density and cell developmental origin, plays an important role in vessel health and fu...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

The many flavors of monocyte/macrophage--endothelial cell interactions
Purpose of review The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages originated directly from embryonic progenitors, populate and establish residency in all tissues examined so far. This review aims to summarize our current understanding on the diversity of monocyte/macrophage subtypes associated with the vasculature, their specific origins, and nature of their cross-talk with the endothelium. Recent findings Taking stock of the many interactions between the endothelium and monocytes/macrophages reveals a f...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe Source Type: research

Effective use of hydroxyurea for sickle cell anemia in low-resource countries
Purpose of review Over the past several decades, hydroxyurea has emerged as a well tolerated and potent disease-modifying therapy for children and adults with sickle cell anemia (SCA). Strong, evidence-based recommendations from the National Institutes of Health, American Society of Hematology, and British Society of Haematology document that hydroxyurea is now standard of care treatment for SCA. In low-resource settings, however, hydroxyurea is rarely utilized due to lack of availability, inadequate treatment guidance, and excessive costs. Recent findings Research trials conducted within the Caribbean and sub-Saharan...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

GATA2 +9.5 enhancer: from principles of hematopoiesis to genetic diagnosis in precision medicine
Purpose of review By establishing mechanisms that deliver oxygen to sustain cells and tissues, fight life-threatening pathogens and harness the immune system to eradicate cancer cells, hematopoietic stem and progenitor cells (HSPCs) are vital in health and disease. The cell biological framework for HSPC generation has been rigorously developed, yet recent single-cell transcriptomic analyses have unveiled permutations of the hematopoietic hierarchy that differ considerably from the traditional roadmap. Deploying mutants that disrupt specific steps in hematopoiesis constitutes a powerful strategy for deconvoluting the comp...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Erythrocyte adaptive metabolic reprogramming under physiological and pathological hypoxia
Purpose of review The erythrocyte is the most abundant cell type in our body, acting as both a carrier/deliverer and sensor of oxygen (O2). Erythrocyte O2 delivery capacity is finely regulated by sophisticated metabolic control. In recent years, unbiased and robust human metabolomics screening and mouse genetic studies have advanced erythroid research revealing the differential role of erythrocyte hypoxic metabolic reprogramming in normal individuals at high altitudes and patients facing hypoxia, such as sickle cell disease (SCD) and chronic kidney disease (CKD). Here we summarize recent progress and highlight potential ...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Current and future gene therapies for hemoglobinopathies
Purpose of review In this work we briefly summarize the key features and currently available conventional therapies for the two main β-hemoglobinopathies, sickle cell disease (SCD) and β-thalassemia, and review the rapidly evolving field of novel and emerging genetic therapies to cure the disease. Recent findings Gene therapy using viral vectors or designer nuclease-based gene editing is a relatively new field of medicine that uses the patient's own genetically modified cells to treat his or her own disease. Multiple different approaches are currently in development, and some have entered phase I clinical st...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

When basic science reaches into rational therapeutic design: from historical to novel leads for the treatment of β-globinopathies
Purpose of review β-hemoglobinopathies, such as β-Thalassemias (β-Thal) and sickle cell disease (SCD) are among the most common inherited genetic disorders in humans worldwide. These disorders are characterized by a quantitative (β-Thal) or qualitative (SCD) defects in adult hemoglobin production, leading to anemia, ineffective erythropoiesis and severe secondary complications. Reactivation of the fetal globin genes (γ-globin), making-up fetal hemoglobin (HbF), which are normally silenced in adults, represents a major strategy to ameliorate anemia and disease severity. Recent findings Followi...
Source: Current Opinion in Hematology - April 3, 2020 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research

Small molecule therapeutics to treat the β-globinopathies
Purpose of review The current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies. Recent findings Recent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies. Summary We summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target ...
Source: Current Opinion in Hematology - April 3, 2020 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, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Distinguishing atypical chronic myeloid leukemia from other Philadelphia-negative chronic myeloproliferative neoplasms
Purpose of review Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative, is a rare myelodysplastic/myeloproliferative neoplasm (MDS/MPN) characterized by leukocytosis, granulocytic dysplasia, and typically poor patient outcomes. Since its first description as a variant CML lacking the Philadelphia chromosome (Ph), the diagnostic criteria for aCML have evolved significantly. Nevertheless, distinguishing it from other Ph-negative myeloid neoplasms can still be very challenging, and given its generally worse prognosis, this is a clinically important distinction. The purpose of this review is to conceptualize our under...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Recent advances in allogeneic hematopoietic cell transplantation for acute myeloid leukemia
Purpose of review Allogeneic hematopoietic cell transplantation (HCT), with associated graft-versus-leukemia effects, remains the best postremission strategy for patients with intermediate or high-risk acute myeloid leukemia (AML), with a curative potential. Here, we highlight recent advances in allogeneic HCT that broadened access, refined prognostication, and improved outcomes of AML patients undergoing this procedure. Recent findings Eligibility for allogeneic HCT continued to expand to AML patients older than 60 years, as well as to patients lacking human leukocyte antigen (HLA)-matched donors with the advent of a...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Relapsed or primary refractory AML: moving past MEC and FLAG-ida
Purpose of review Treatment of relapsed and refractory acute myeloid leukemia (AML) is still very challenging, with poor response rates and low chance for cure. This is especially true when treating patients who are elderly, have multiple comorbidities, or who are too unfit for traditional salvage chemotherapy regimens. Recent findings Recently, advances in the treatment of relapsed/refractory AML utilizing novel chemotherapy combinations, hypomethylating, and targeted therapies have shown promising results. Summary Several early-phase studies with novel targeted therapy combinations have demonstrated encouraging r...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Blastic plasmacytoid dendritic cell neoplasm: diagnosis, manifestations, and treatment
Purpose of review Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes. It typically manifests as asymptomatic skin lesions and cytopenias, which result from bone marrow involvement. Less commonly, it will present in lymph nodes or visceral organs as well. Although rare, BPDCN has been discussed more frequently in recent years as new drugs have been developed that could be effective at treating this disease. Recent findings Until recently, treatment for BPDCN commonly included intensive chemotherapy regimens, which are generally reserved f...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Optimal therapeutic strategies for mixed phenotype acute leukemia
Purpose of review Mixed phenotype acute leukemia (MPAL) encompasses a rare group of clinically, immunophenotypically, and genetically diverse leukemias. Diagnosing and treating these patients remains challenging. In recent years, systematic efforts have been made to better define the genetic landscape of MPAL. These insights allow better understanding of the pathophysiology of MPAL, have the potential for a more biologically meaningful classification and may promote targeted, novel approaches to treat these leukemias. Recent findings Recent studies suggest that MPALs originate in a multipotent primitive cell, demonstr...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Myeloid sarcoma
Purpose of review Myeloid sarcoma; also known as granulocytic sarcoma and chloroma, often occurs concomitantly with AML, and rarely without bone marrow involvement. In this article, we review the recent literature on myeloid sarcoma, focusing on treatment approach for this rare disease, and addressing the prognostic and therapeutic role of molecular and cytogenetic aberrations. Recent findings Molecular testing and cytogenetics are important adjunct to conventional diagnostic methods. The significance of cytogenetic and molecular abnormalities in myeloid sarcoma is not completely established, but testing for targetabl...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Detection and management of acute myeloid leukemia measurable residual disease: is it standard of care?
Purpose of review In the present manuscript, we will review the current approaches to investigate measurable residual disease (MRD) and its clinical applications in AML management. Recent findings Over the last decades, several methods have been developed to trace MRD, with flow cytometry and polymerase chain reaction (PCR) being the most reliable. However, new technologies, such as digital PCR and Next-Generation Sequencing are emerging as particularly useful in AML. The 2017 European LeukemiaNet (ELN) recommendations have incorporated MRD assessment to define the response criteria to therapy, and more recently, the ...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Hypomethylating agents with venetoclax: have we discovered the holy grail?
Purpose of review Since its approval in November 2018, venetoclax with a hypomethylating agent backbone has shown promising efficacy for older, newly diagnosed acute myeloid leukemia (AML) patients who are unfit for standard intensive induction chemotherapy. This regimen is well tolerated, allows for deep and durable responses and may be increasing the prevalence of the disease. Although there is justifiable excitement, it remains to be seen to what extent venetoclax-based regimens, as they are currently administered, will have a long-term impact on the treatment of AML. This review aims to evaluate the strengths of the ...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Tumor protein 53 mutations in acute myeloid leukemia: conventional induction chemotherapy or novel therapeutics
Purpose of review Tumor protein 53 (TP53) protein is involved in fundamental processes of cancer, aging, and DNA repair. Thus, TP53 dysfunction is implicated in malignant processes and remains the most commonly mutated gene in cancer but represents a relatively small proportion in acute myeloid leukemia (AML). Patients with TP53-mutated AML attain inferior responses to therapy resulting in poor overall outcomes. Recent findings Traditional treatment approaches with conventional chemotherapy yields suboptimal responses for patients with TP53 mutant AML compared with wildtype TP53. In recent years, there is increasing i...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Novel therapies in myelodysplastic syndromes
Purpose of review Currently, there is a rapid expansion of novel, efficacious therapies for the treatment of patients with myelodysplastic syndromes (MDS) at a rate never seen to date. In this review, we will outline new treatment strategies in MDS focusing on novel hypomethylating agents (HMA) and combinations in addition to targeted and immune-based therapies. Recent findings Large-scale gene sequencing and immune-based research has given us a great deal of information regarding the complexity and heterogeneity of MDS. This rapid improvement in our knowledge has provided a framework for development of novel therapie...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Driver mutations in acute myeloid leukemia
Purpose of review The mutational landscape of acute myeloid leukemia (AML) has revised diagnostic, prognostic, and therapeutic schemata over the past decade. Recurrently mutated AML genes have functional consequences beyond typical oncogene-driven growth and loss of tumor suppresser function. Recent findings Large-scale genomic sequencing efforts have mapped the complexity of AML and trials of mutation-based targeted therapy has led to several FDA-approved drugs for mutant-specific AML. However, many recurrent mutations have been identified across a spectrum from clonal hematopoiesis to myelodysplasia to overt AML, su...
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 30, 2020 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research

Myeloid cell and cytokine interactions with chimeric antigen receptor-T-cell therapy: implication for future therapies
Purpose of review Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary tool in the treatment of cancer. CAR-T cells exhibit their effector functions through the recognition of their specific antigens on tumor cells and recruitment of other immune cells. However, this therapy is limited by the development of severe toxicities and modest antitumor activity in solid tumors. The host and tumor microenvironment interactions with CAR-T cells play an important role in orchestrating CAR-T-cell functions. Specifically, myeloid lineage cells and their cytokines critically influence the behavior of CAR-T cells. Here, w...
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Platelets as key players in inflammation and infection
Purpose of review This review highlights recent insights into the role of platelets in acute inflammation and infection. Recent findings Platelets exhibit intravascular crawling behavior and can collect and bundle bacteria. In addition, platelets are key in promoting intravascular thrombus formation in infection, a process termed ‘immunothrombosis’, which contributes to pathogen containment, but also potentially damages the host. Platelets are at the nexus of leukocyte recruitment and activation, yet they are at the same time crucial in preventing inflammation-associated hemorrhage and tissue damage. This ...
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Transcription factor and cytokine regulation of eosinophil lineage commitment
Purpose of review Lineage commitment is governed by instructive and stochastic signals, which drive both active induction of the lineage program and repression of alternative fates. Eosinophil lineage commitment is driven by the ordered interaction of transcription factors, supported by cytokine signals. This review summarizes key findings in the study of eosinophil lineage commitment and examines new data investigating the factors that regulate this process. Recent findings Recent and past studies highlight how intrinsic and extrinsic signals modulate transcription factor network and lineage decisions. Early action o...
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Registries for study of nonmalignant hematological diseases: the example of the Severe Chronic Neutropenia International Registry
This report describes underlying reasons for its success. Summary Registries are important to organize and analyze clinical information across geographic, ethnic and social boundaries. They are also challenging to organize, administer and support. (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Family studies of warts, hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome
Purpose of review WHIM syndrome (warts, hypogammaglobulinemia, immunodeficiency, myelokathexis, or WHIMs) is a very rare autosomal dominant immunodeficiency disorder attributable to mutations in CXCR4. We reviewed clinical manifestations in 24 patients in 9 families to expand understanding of this syndrome. Recent findings Warts, cellulitis and respiratory infections are common in patients with WHIMs. Less commonly these patients have congenital heart disease, human papilloma virus-associated malignancies (cervical and vulvular) and lymphomas. Hearing loss because of recurrent otitis media is another important complic...
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Genetic and epigenetic factors interacting with clonal hematopoiesis resulting in chronic myelomonocytic leukemia
Purpose of review Since 2016, the WHO has recognized the significant phenotypic heterogeneity of chronic myelomonocytic leukemia (CMML) as a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap disease. Although sharing many somatic mutations with MDS and MPN, the purpose of this review is to put recent biological findings of CMML in the context of evolutionary theory, highlighting it as a distinct evolutionary trajectory occurring in the context of clonal hematopoiesis. Recent findings Clonal hematopoiesis of indeterminate potential (CHIP), with a mutational spectrum and prevalence correlated with a...
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Commentary
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - November 29, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research