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Current Opinion in Hematology

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https://www.readbyqxmd.com/read/28212190/endothelial-cell-disease-emerging-knowledge-from-cerebral-cavernous-malformations
#1
Maria Grazia Lampugnani, Matteo Malinverno, Elisabetta Dejana
PURPOSE OF REVIEW: Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke...
February 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212189/wnt-signaling-in-the-vessel-wall
#2
Lina Badimon, Maria Borrell-Pages
PURPOSE OF REVIEW: Wnt signaling plays a crucial role during embryogenesis. In an adult, Wnt is mainly associated to cellular proliferation and differentiation mechanisms. Recent data suggest that Wnt signaling is involved in the pathophysiology of atherosclerosis. However, the roles of Wnt signaling pathways in the vessel wall are poorly understood. This review outlines recent discoveries in understanding the role of Wnt pathways in healthy and atherosclerotic vessels. RECENT FINDINGS: In the last years, the involvement of both canonical and noncanonical Wnt pathways in the development of atherosclerotic lesions has been recognized...
February 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212192/genetic-control-of-erythropoiesis
#3
Laxminath Tumburu, Swee Lay Thein
PURPOSE OF REVIEW: The discovery of several genetic variants associated with erythroid traits and subsequent elucidation of their functional mechanisms are exemplars of the power of the new genetic and genomic technology. The present review highlights findings from recent genetic studies related to the control of erythropoiesis and dyserythropoiesis, and fetal hemoglobin, an erythroid-related trait. RECENT FINDINGS: Identification of the genetic modulators of erythropoiesis involved two approaches: genome-wide association studies (GWASs) using single nucleotide polymorphism (SNP) arrays that revealed the common genetic variants associated with erythroid phenotypes (hemoglobin, red cell count, MCV, MCH) and fetal hemoglobin; and massive parallel sequencing such as whole genome sequencing (WGS) and whole exome sequencing (WES) that led to the discovery of the rarer variants (GFI1B, SBDS, RPS19, PKLR, EPO, EPOR, KLF1, GATA1)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#4
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28178039/rap1-in-endothelial-biology
#5
Magdalena Chrzanowska-Wodnicka
PURPOSE OF REVIEW: Ubiquitously-expressed small GTPase Rap1 is a key modulator of integrin- and cadherin-regulated processes. In endothelium, Rap1 promotes angiogenesis and endothelial barrier function, acting downstream from cAMP-activated Rap1GEF, Epac. Recent in-vivo studies in mouse models have provided more information about the physiological role of Rap1 in vessel development and after birth under normal and pathologic conditions. Important molecular details of dynamic regulation of endothelial barrier are uncovered...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#6
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28157724/orchestration-of-late-events-in-erythropoiesis-by-klf1-eklf
#7
Merlin Nithya Gnanapragasam, James J Bieker
PURPOSE OF REVIEW: Transcriptional regulators provide the molecular and biochemical basis for the cell specific properties and characteristics that follow from their central role in establishing tissue-restricted expression. Precise and sequential control of terminal cell divisions, nuclear condensation, and enucleation are defining characteristics within erythropoietic differentiation. This review is focused on KLF1, a central global regulator of this process. RECENT FINDINGS: Studies in the past year have brought a number of proteins that are targets of KLF1 regulation into focus with respect to their roles in terminal erythroid differentiation...
February 2, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28118224/acute-hepatic-and-erythropoietic-porphyrias-from-ala-synthases-1-and-2-to-new-molecular-bases-and-treatments
#8
Hana Manceau, Laurent Gouya, Hervé Puy
PURPOSE OF REVIEW: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies...
January 21, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28118223/rna-splicing-during-terminal-erythropoiesis
#9
John G Conboy
PURPOSE OF REVIEW: Erythroid progenitors must accurately and efficiently splice thousands of pre-mRNAs as the cells undergo extensive changes in gene expression and cellular remodeling during terminal erythropoiesis. Alternative splicing choices are governed by interactions between RNA binding proteins and cis-regulatory binding motifs in the RNA. This review will focus on recent studies that define the genome-wide scope of splicing in erythroblasts and discuss what is known about its regulation...
January 21, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28118222/maintenance-and-regulation-of-asymmetric-phospholipid-distribution-in-human-erythrocyte-membranes-implications-for-erythrocyte-functions
#10
Nobuto Arashiki, Yuichi Takakuwa
PURPOSE OF REVIEW: The article summarizes new insights in the molecular mechanisms for the maintenance and regulation of the asymmetric distribution of phospholipids in human erythrocyte membranes. We focus on phosphatidylserine, which is primarily found in the inner leaflet of the membrane lipid bilayer under low Ca conditions (<1 μmol/l) and is exposed to the outer leaflet under elevated Ca concentrations (>1 μmol/l), when cells become senescent. Clarification of the molecular basis of phosphatidylserine flipping and scrambling is important for addressing long-standing questions regarding phosphatidylserine functions...
January 21, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099275/characterization-regulation-and-targeting-of-erythroid-progenitors-in-normal-and-disordered-human-erythropoiesis
#11
Brian M Dulmovits, Jimmy Hom, Anupama Narla, Narla Mohandas, Lionel Blanc
PURPOSE OF REVIEW: The erythroid progenitors burst-forming unit-erythroid and colony-forming unit-erythroid have a critical role in erythropoiesis. These cells represent a heterogeneous and poorly characterized population with modifiable self-renewal, proliferation and differentiation capabilities. This review focuses on the current state of erythroid progenitor biology with regard to immunophenotypic identification and regulatory programs. In addition, we will discuss the therapeutic implications of using these erythroid progenitors as pharmacologic targets...
January 21, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28072603/dyserythropoiesis-of-myelodysplastic-syndromes
#12
Carine Lefèvre, Sabrina Bondu, Salomé Le Goff, Olivier Kosmider, Michaela Fontenay
PURPOSE OF REVIEW: Myelodysplastic syndromes (MDS) are heterogeneous diseases of the hematopoietic stem cell in the elderly. Anemia is the main symptom that mostly correlates with dysplastic erythropoiesis in the bone marrow. We will review the recent advances in understanding the diverse mechanisms of dyserythropoiesis. RECENT FINDINGS: Dyserythropoiesis defined as 10% dysplastic erythroid cells in the bone marrow is found in more than 80% of early MDS. Immature erythroblasts accumulate at the expense of mature erythroblasts due to differentiation arrest and apoptosis...
January 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28141615/editorial-introduction
#13
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099274/can-any-patients-with-chronic-myeloid-leukemia-outside-of-a-clinical-trial-have-their-tyrosine-kinase-inhibitor-discontinued
#14
Michael J Mauro
PURPOSE OF REVIEW: This article critically appraises the state of treatment-free remission as a strategy for patients with chronic myeloid leukemia (CML) in deep remission after therapy with tyrosine kinase inhibitors (TKIs). RECENT FINDINGS: Approximately half of patients with CML defined fairly narrowly by trial criteria - TKI sensitive, in deep molecular remission for a defined period - can successfully maintain protective levels of response after TKI cessation...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099273/making-the-most-of-hypomethylating-agents-in-myelodysplastic-syndrome
#15
Geetika Bhatt, William Blum
PURPOSE OF REVIEW: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. RECENT FINDINGS: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability)...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099272/mixed-phenotype-acute-leukemia-current-challenges-in-diagnosis-and-therapy
#16
Ofir Wolach, Richard M Stone
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099271/innovative-strategies-for-adverse-karyotype-acute-myeloid-leukemia
#17
Sabine Blum, Gabriele Greve, Michael Lübbert
PURPOSE OF REVIEW: Adverse karyotype acute myeloid leukemia is a disease particularly of older patients, but also observed in younger patients. Despite all efforts, standard chemotherapy is still generally applied in fit patients, as already for decades, and for nearly all different subtypes of acute myeloid leukemia. Lack of more specifically targeted therapy and the often older age of the patients are complicating treatment, and in the subgroup of patients achieving a complete remission, the strikingly high frequency of relapse is a characteristic of this disease...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28072602/-jak-ing-up-the-treatment-of-primary-myelofibrosis-building-better-combination-strategies
#18
Rita Assi, Srdan Verstovsek, Naval Daver
PURPOSE OF REVIEW: The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors-based combinatorial strategies in this setting. RECENT FINDINGS: Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of life, and an overall survival advantage with prolonged follow-up...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28030373/what-are-the-most-promising-new-agents-in-acute-myeloid-leukemia
#19
David A Sallman, Jeffrey E Lancet
PURPOSE OF REVIEW: Although the treatment paradigm for acute myeloid leukemia (AML) had been largely unchanged for many years, in-depth molecular characterization has revolutionized our understanding of mutations that drive the disease, subsequently serving to guide current clinical investigation. Furthermore, recent advances in the field have highlighted the importance of optimizing known efficacious agents by improving drug delivery or bypassing resistance mechanisms. The current status of novel agents which are shaping the clinical management of AML patients are summarized in this review...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#20
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
March 2017: Current Opinion in Hematology
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