Microenvironment signaling driving lymphomagenesis
Purpose of review In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment. Recent findings Lymphoma supportive niche integrates a dynamic and orchestrated network of immune and...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Precision medicine and lymphoma
Purpose of review The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment. Recent findings DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity. Recent studies have seen advances in the stratification of germinal center lymphomas, through comprehensive profiling of 100...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Three-dimensional genome organization in normal and malignant haematopoiesis
Purpose of review The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer–promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners. Here we discuss recent ...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

DNA damage pathways and B-cell lymphomagenesis
Purpose of review Recent lymphoma genome sequencing projects have shed light on the genomic landscape of indolent and aggressive lymphomas, as well as some of the molecular mechanisms underlying recurrent mutations and translocations in these entities. Here, we review these recent genomic discoveries, focusing on acquired DNA repair defects in lymphoma. In addition, we highlight recently identified actionable molecular vulnerabilities associated with recurrent mutations in chronic lymphocytic leukemia (CLL), which serves as a model entity. Recent findings The results of several large lymphoma genome sequencing project...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Genetic convergence of rare lymphomas
Purpose of review We review the genetic foundations of different rare lymphomas to examine their shared origins. These data indicate the potential application of genomics to improve the diagnosis and treatment of these rare diseases. Recent findings Next generation sequencing technologies have provided an important window into the genetic underpinnings of lymphomas. A growing body of evidence indicates that although some genetic alterations are specific to certain diseases, others are shared across different lymphomas. Many such genetic events have already demonstrated clinical utility, such as BRAF V600E that confers...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

SOX11, a key oncogenic factor in mantle cell lymphoma
Purpose of review SOX11 has emerged as a key transcription factor in the pathogenesis of mantle cell lymphoma (MCL) whereas it is not expressed in normal B cells or virtually in any other mature B-cell neoplasm. This review will examine the role of SOX11 as a biomarker in MCL, the new information on its transcriptional targets, and the mechanisms regulating its expression in MCL. Recent findings SOX11 is highly expressed in conventional MCL, including cyclin D1-negative cases, but it is not expressed in the indolent leukemic nonnodal MCL subtype. These two MCL subtypes also differ in their cell-of-origin, IGHV mutatio...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: LYMPHOID BIOLOGY AND DISEASES: Edited by Ari Melnick Source Type: research

Transcription factors FOXO in the regulation of homeostatic hematopoiesis
Purpose of review Work in the past decade has revealed key functions of the evolutionary conserved transcription factors Forkhead box O (FOXO) in the maintenance of homeostatic hematopoiesis. Here the diverse array of FOXO functions in normal and diseased hematopoietic stem and progenitor cells is reviewed and the main findings in the past decade are highlighted. Future work should reveal FOXO-regulated networks whose alterations contribute to hematological disorders. Recent findings Recent studies have identified unanticipated FOXO functions in hematopoiesis including in hematopoietic stem and progenitor cells (HSPC)...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

The crosstalk between hematopoietic stem cells and their niches
Purpose of review Hematopoietic stem cells (HSCs) reside in specific microenvironments also called niches that regulate HSC functions. Understanding the molecular and cellular mechanisms involved in the crosstalk between HSCs and niche cells is a major issue in stem cell biology and regenerative medicine. The purpose of this review is to discuss recent advances in this field with particular emphasis on the transcriptional landscape of HSC niche cells and the roles of extracellular vesicles (EVs) in the dialog between HSCs and their microenvironments. Recent findings The development of high-throughput technologies comb...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Exosomes in acute myeloid leukemia inhibit hematopoiesis
Purpose of review Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML). Recent findings Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC. Furthermore, exosomes secreted by AML blasts...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Advances in the role of the aryl hydrocarbon receptor to regulate early hematopoietic development
Purpose of review We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the production of clinically relevant blood products suitable for patient care. Recent findings Initial data demonstrate that both pharmacologic AHR inhibition and genetic deletion from human pluripotent stem cells provide useful strategies to enhance the yield of hematopoietic stem and progenitor cells. AHR hyperactivation following the induction of CD34+ megakaryocyte–erythr...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Latexin and hematopoiesis
Purpose of review Hematopoietic stem cells (HSCs) produce mature blood cells throughout lifetime. Natural genetic diversity offers an important yet largely untapped reservoir for deciphering regulatory mechanisms of HSCs and hematopoiesis. In this review, we explore the role of latexin, identified by natural variation, in regulating homeostatic and stress hematopoiesis, unravel the underlying signaling pathways, and propose its therapeutic implication. Recent findings Latexin acts endogenously in HSCs to negatively regulate their population size by enhancing apoptosis and by decreasing self-renewal. Deletion of latexi...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Cohesin in haematopoiesis and leukaemia
Purpose of review Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin has become increasingly recognized. In this review, we will focus on the role of the chromatin organizing protein complex cohesin in regulation of normal and malignant haematopoiesis. Recent findings Several functional studies...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

ETS transcription factor ETV2/ER71/Etsrp in haematopoietic regeneration
Purpose of review Recent studies have established that haematopoietic stem cells (HSCs) remain quiescent in homeostatic conditions, and minimally contribute to haematopoietic homeostasis. However, they undergo extensive cell cycle and expansion upon bone marrow transplantation or haematopoietic injury to reestablish the haematopoietic system. Molecular basis for the HSC activation and expansion is not completely understood. Here, we review the recent study elucidating the role of the developmentally critical Ets transcription factor Etv2 in reestablishing haematopoietic system upon injury through promoting HSC regenerati...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Enhancing human cord blood hematopoietic stem cell engraftment by targeting nuclear hormone receptors
Purpose of review Allogeneic hematopoietic cell transplantation (HCT) is a life-saving therapy for hematological and nonhematological diseases. Cord blood is a source of transplantable hematopoietic stem cells (HSCs), but limited numbers of HSCs in single cord blood units, which may cause delayed neutrophil, platelet, and immune cell reconstitution, is a major problem for efficient transplantation. Ex-vivo expansion and enhanced homing of cord blood HSC may overcome this disadvantage and improve its long-term engraftment. Here, we discuss the role of nuclear hormone receptors signaling in human cord blood HSC engraftment...
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - June 7, 2018 Category: Hematology Tags: Editorial Introductions Source Type: research

Endothelial cell biology of Endoglin in hereditary hemorrhagic telangiectasia
Purpose of review Mutations in the Endoglin (Eng) gene, an auxiliary receptor in the transforming growth factor beta (TGFβ)-superfamily signaling pathway, are responsible for the human vascular disorder hereditary hemorrhagic telangiectasia (HHT) type 1, characterized in part by blood vessel enlargement. A growing body of work has uncovered an autonomous role for Eng in endothelial cells. We will highlight the influence of Eng on distinct cellular behaviors, such as migration and shape control, which are ultimately important for the assignment of proper blood vessel diameters. Recent findings How endothelial cell...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

MicroRNAs in endothelial cell homeostasis and vascular disease
Purpose of review Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction. Recent findings MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Endothelial cell protein C receptor-dependent signaling
Purpose of review Endothelial cell protein C receptor (EPCR), a transmembrane glycoprotein present on the surface of endothelial cells and other cell types, is an essential component of the protein C (PC) anticoagulant system. EPCR is also shown to play a critical role in mediating activated protein C (APC)-induced cytoprotective signaling. The purpose of this review is to outline the mechanisms of EPCR-dependent cell signaling and discuss recent findings made in this area. Recent findings Recent studies showed that the cleavage of protease-activated receptor (PAR)1 at a noncanonical site by APC–EPCR or the cano...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

NOTCH regulation of the endothelial cell phenotype
Purpose of review The formation of a hierarchical vascular network is a complex process that requires precise temporal and spatial integration of several signaling pathways. Amongst those, Notch has emerged as a key regulator of multiple steps that expand from endothelial sprouting to arterial specification and remains relevant in the adult. This review aims to summarize major concepts and rising hypotheses on the role of Notch signaling in the endothelium. Recent findings A wealth of new information has helped to clarify how Notch signaling cooperates with other pathways to orchestrate vascular morphogenesis, branchi...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Recent insights into vascular development from studies in zebrafish
Purpose of review Zebrafish has provided a powerful platform to study vascular biology over the past 25 years, owing to their distinct advantages for imaging and genetic manipulation. In this review, we summarize recent progress in vascular biology with particular emphasis on vascular development in zebrafish. Recent findings The advent of transcription activator-like effector nuclease and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome-editing technologies has dramatically facilitated reverse genetic approaches in zebrafish, as in other models. Here, we highlight ...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Contribution of resident and recruited macrophages in vascular physiology and pathology
Purpose of review Macrophages are generally believed to originate entirely from the bone marrow; however, this paradigm is challenged by the discovery of yolk-sac-derived resident macrophages. Here, we provide an overview of recent advances in the ontogeny and function of resident macrophages. Recent findings Macrophage precursors from three distinct embryonic sources (yolk sac, fetal liver and bone marrow) are found to colonize various tissues via the blood circulation early during embryogenesis until shortly after birth. They differentiate into distinct long-lived resident macrophages in response to the expression o...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: VASCULAR BIOLOGY: Edited by Edward F. Plow Source Type: research

Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells
Purpose of review Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood. This review focuses on the current state of erythroid biology in regards to EPO si...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

The flux of iron through ferritin in erythrocyte development
Purpose of review Terminal differentiation of erythropoietic progenitors requires the rapid accumulation of large amounts of iron, which is transported to the mitochondria, where it is incorporated into heme. Ferritin is the sole site of iron storage present in the cytosol. Yet the role of iron accumulation into ferritin in the context of red cell development had not been clearly defined. Early studies indicated that at the onset of terminal differentiation, iron initially accumulates in ferritin and precedes heme synthesis. Whether this accumulation is physiologically important for red cell development was unclear until...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Hemolysis and immune regulation
Purpose of review Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders. Recent findings Plasma-free heme can induce the formation of neutrophil extracellular traps (NETs) through reactive oxygen species signaling. Although NETs protect the host against infection...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Clinical manifestations of sickle cell disease in India: misconceptions and reality
Purpose of review In the past, milder clinical manifestations of sickle cell disease (SCD) have been described from India. However, recent data from some parts of India suggest that the severity of the disease can be compared to that of African phenotypes. This review therefore describes the varied clinical manifestation of SCD, the success of newborn screening programme, prenatal diagnosis and low dose hydroxyurea therapy in India. Recent findings The varied clinical manifestations such as anemia, vaso-occlusive crisis, acute chest syndrome, renal involvement, stroke and so on vary from one part of the country to the...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Band 3 function and dysfunction in a structural context
Purpose of review Current research on the human band 3 glycoprotein, the red cell chloride/bicarbonate anion exchanger (AE1), is highlighted and placed within a structural context. Recent Findings The determination of the crystal structure of the membrane domain of human band 3, the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters, is a major breakthrough toward understanding the mechanism of action of this membrane transport protein, its interaction with partner proteins, and how mutations linked to disease affect its ability to fold and function. Summary Band 3 contains 14 transme...
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 5, 2018 Category: Hematology Tags: Editorial Introductions Source Type: research

Resistance in chronic myeloid leukemia: definitions and novel therapeutic agents
Purpose of review Chronic myeloid leukemia (CML) is hallmarked by the presence of fusion protein kinase derived from a reciprocal translocation between chromosome 9 and 22, breakpoint cluster region (BCR)–Abelson leukemia virus (ABL) 1, causing aberrant regulation of the downstream pathways leading to unchecked CML leukemia stem cells (LSCs) proliferation. Since the discovery of tyrosine kinase inhibitors (TKI), CML, once a fatal disease, has become a chronic illness if managed appropriately. Changing treatment landscape has unsurfaced the challenge of TKI resistance that is clinically difficult to overcome. Recen...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes
Purpose of review Hypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy. Recent findings Recent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alt...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors
Purpose of review This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). Recent findings The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in ma...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Driver mutations in primary myelofibrosis and their implications
Purpose of review Primary myelofibrosis (PMF) is one of the classic BCR-ABL1 negative myeloproliferative neoplasms (MPN). Oncogenic driver mutations in PMF include Janus kinase 2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene. These mutations are not only pathogenetically relevant but might also influence disease outcome. Our objective for the current communication is to comprehensively review the distinct phenotypic, therapeutic, and prognostic implications of driver mutations in PMF. Recent findings The discovery of driver mutations has revolutionized our understanding of pathogenic mechanisms ...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Changes in the World Health Organization 2016 classification of myeloid neoplasms everyone should know
Purpose of review This review highlights the main changes in the revised 2016 WHO classification of myeloid neoplasms (published in 2017) that impact diagnosis and ultimately impact management of patients with these diseases. Recent findings The revision was based on data accumulated since the 2008 WHO classification, much of which relate to new molecular genetic information about these neoplasms. This massive recent influx of data concerning the significance of pathogenic mutations has affected all myeloid neoplasm categories. The new information has been incorporated as part of the diagnostic criteria of many diseas...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Polycythemia vera and essential thrombocythemia: algorithmic approach
Purpose of review To describe an algorithm-based approach, whenever available, to the diagnosis, the risk stratification criteria informing therapy and the current management of polycythemia vera and essential thrombocythemia. Recent findings Description of recurrent genetic abnormalities in driver genes, including Janus Kinase 2 (JAK2), myeloproliferative leukemia and calreticulin, a better appreciation of the key diagnostic role of bone marrow features, results of large epidemiologic studies and a few but landmark controlled clinical trials produced in the last decade, all resulted in a reappraisal of the approach t...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Have haploidentical transplants replaced umbilical cord transplants for acute leukemias?
Purpose of review Haploidentical stem cell transplantation (Haplo SCT) and umbilical cord blood stem cell transplantation (UCB SCT) have emerged over the past two to three decades as viable sources of alternative donor SCT when a human leukocyte antigen matched donor is not available. However, which of these two donor types is optimal for patients with leukemia in need of allografting is unknown. Recent findings For patients with acute leukemia, results of UCB SCT have been improved by the use of double umbilical cord units and emerging ex-vivo expansion technologies. However, the costs associated with procuring doubl...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Revisiting autologous transplantation in acute myeloid leukemia
Purpose of review Autologous hematopoietic cell transplantation (auto-HCT) has been evaluated as a consolidation treatment for acute myeloid leukemia (AML) in the 1980s and 1990s. These prospective studies from large trials compared auto-HCT with chemotherapy. A comparison was made also with allogeneic hematopoietic cell transplantation (allo-HCT). These studies reported a lower relapse rate with auto-HCT compared with chemotherapy, but without impact on the overall survival. A high transplant-related mortality in that era confounded the relevance of these data. Recent findings Several prospective studies and a pletho...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

New therapeutic strategies for high-risk acute myeloid leukemia
Purpose of review Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease. Recent findings Induction therapy is in the process of changing for several patient populations. The introduction of CPX-351 offers a novel strategy for treating patients with therapy-related AML or AML with myelodysplas...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

The most novel of the novel agents for acute myeloid leukemia
Purpose of review Precious few drugs were successfully developed for acute myeloid leukemia (AML) over the past decades, despite a dramatic expansion of our understanding of its molecular underpinnings during this time. Then in 2017, a wave of new drugs suddenly became approved. This review serves to introduce the newly available drugs, discuss their impact upon therapy, and highlight additional novel agents that are waiting in the wings. Recent findings Newly approved agents in AML include a tyrosine kinase inhibitor for patients with FMS-like tyrosine kinase 3 (FLT3) mutations, an inhibitor of mutant isocitrate dehy...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

When should patients receive consolidation chemotherapy before allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission?
Purpose of review Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT. Recent findings Randomized controlled studies are lacking. Data derive largely from four large retrospective registry studies. These analyses are consistent in demonstrating the lack of any survival ...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions
We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including ‘7+3 Plus’ combinations. Summary Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrat...
Source: Current Opinion in Hematology - February 1, 2018 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research

Cohesin mutations in myeloid malignancies made simple
Purpose of review Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer Recent findings The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division. Although initially...
Source: Current Opinion in Hematology - February 1, 2018 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 - February 1, 2018 Category: Hematology Tags: Editorial Introduction Source Type: research

Metabolic regulation of macrophages in tumor microenvironment
Purpose of review Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. Recent findings Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells. However, the Warburg effect has recently been proven to exist in various types of immune cells in ...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

The regulation and importance of monocyte chemoattractant protein-1
Purpose of review Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition. Recent findings Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/mac...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Dysregulated myelopoiesis and hematopoietic function following acute physiologic insult
Purpose of review The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. Recent findings Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term fu...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity
Purpose of review Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Recent findings Although agranulocytosis and cutaneous vasculitis...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring
Purpose of review Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species – nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed. Recent findings The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine &nd...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae
Purpose of review Gonorrhea is a major global health concern, caused by the bacterium Neisseria gonorrhoeae. The main clinical feature of acute gonorrhea is neutrophilic influx that is unable to clear infection. Women of reproductive age are predominantly at risk for serious sequelae of gonorrhea, including pelvic inflammatory disease, ectopic pregnancy, and infertility. This review will highlight how neutrophils are recruited to the female reproductive tract (FRT) in response to N. gonorrhoeae, how N. gonorrhoeae resists killing by neutrophils, and the connection between neutrophilic inflammation and cellular damage. R...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Long-term observational studies of chronic granulomatous disease
Purpose of review Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients. Recent findings For years, CGD is a known cause of life-threatening infections...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Green neutrophilic inclusions: current understanding and review of literature
Purpose of review Green cytoplasmic inclusions in neutrophils are an uncommon finding on the peripheral blood smear. A comprehensive review of the literature is presented here with the goal of summarizing knowledge to date and increasing awareness. Recent findings A total of 41 cases have been reported in the literature, indicating the rarity of these green neutrophilic inclusions. Clinically, the inclusions have most consistently been associated with elevated transaminases, hepatic failure, and a high early mortality rate. The precise composition of the inclusions has not been confirmed. Summary Clinicians, hemato...
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research

Editorial: myeloid biology issue 2018
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - January 1, 2018 Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research