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Current Opinion in Hematology

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https://www.readbyqxmd.com/read/29782339/transcription-factors-foxo-in-the-regulation-of-homeostatic-hematopoiesis
#1
Vijay Menon, Saghi Ghaffari
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), erythroid cells, and immune cells...
May 17, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29746265/microenvironment-signaling-driving-lymphomagenesis
#2
Léa Verdière, Frédéric Mourcin, Karin Tarte
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...
May 8, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29738334/precision-medicine-and-lymphoma
#3
James A Heward, Emil A Kumar, Koorosh Korfi, Jessica Okosun, Jude Fitzgibbon
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...
May 5, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29738333/sox11-a-key-oncogenic-factor-in-mantle-cell-lymphoma
#4
Renée Beekman, Virginia Amador, Elias Campo
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...
May 5, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29702524/genetic-convergence-of-rare-lymphomas
#5
Jennifer R Shingleton, Sandeep S Dave
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...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29702523/the-crosstalk-between-hematopoietic-stem-cells-and-their-niches
#6
Charles Durand, Pierre Charbord, Thierry Jaffredo
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...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29702522/three-dimensional-genome-organization-in-normal-and-malignant-haematopoiesis
#7
Sergi Cuartero, Matthias Merkenschlager
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...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29702521/dna-damage-pathways-and-b-cell-lymphomagenesis
#8
Gero Knittel, Tim Rehkämper, Pascal Nieper, Anna Schmitt, Ruth Flümann, H Christian Reinhardt
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...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29697486/ets-transcription-factor-etv2-er71-etsrp-in-haematopoietic-regeneration
#9
Kyunghee Choi
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 regeneration...
April 24, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29697485/advances-in-the-role-of-the-aryl-hydrocarbon-receptor-to-regulate-early-hematopoietic-development
#10
Mathew G Angelos, Dan S Kaufman
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...
April 24, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29697484/cohesin-in-haematopoiesis-and-leukaemia
#11
Roman Galeev, Jonas Larsson
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...
April 24, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29608488/latexin-and-hematopoiesis
#12
Cuiping Zhang, Ying Liang
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...
March 31, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29608487/enhancing-human-cord-blood-hematopoietic-stem-cell-engraftment-by-targeting-nuclear-hormone-receptors
#13
Bin Guo, Xinxin Huang, Hal E Broxmeyer
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...
March 31, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29547400/micrornas-in-endothelial-cell-homeostasis-and-vascular-disease
#14
Carlos Fernández-Hernando, Yajaira Suárez
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 as potential therapeutic targets for vascular disease...
March 14, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29547401/notch-regulation-of-the-endothelial-cell-phenotype
#15
Julia J Mack, M Luisa Iruela-Arispe
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, branching, and function...
May 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29465435/clinical-manifestations-of-sickle-cell-disease-in-india-misconceptions-and-reality
#16
Dipty Jain, Dipika Mohanty
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 other and also among different communities of India...
May 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29461260/hemolysis-and-immune-regulation
#17
Hui Zhong, Karina Yazdanbakhsh
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...
May 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29461259/the-flux-of-iron-through-ferritin-in-erythrocyte-development
#18
Caroline C Philpott
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...
May 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29461258/endothelial-cell-protein-c-receptor-dependent-signaling
#19
Usha R Pendurthi, L Vijaya Mohan Rao
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 canonical site by thrombin when PC occupies EPCR induces β-arrestin-2-mediated biased cytoprotective signaling...
May 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29438260/endothelial-cell-biology-of-endoglin-in-hereditary-hemorrhagic-telangiectasia
#20
Wade W Sugden, Arndt F Siekmann
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...
May 2018: Current Opinion in Hematology
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