scholarly journals Chronic Eosinophilic Leukaemia Associated with JAK2 Exon 13 Insertion/Deletion Mutations

2021 ◽  
pp. 1-6
Author(s):  
Nicholas Lafferty ◽  
Matthew Salmon ◽  
Nicholas C.P. Cross ◽  
Iain Singer ◽  
Aaron Cooney ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Driver Mutations ◽  
Rare Mutation ◽  
Indel Mutation ◽  
Not Otherwise Specified ◽  
Disease Subtypes ◽  
Specific Association ◽  
Eosinophilic Disorders ◽  
Made In

Chronic eosinophilic leukaemia, not otherwise specified (CEL, NOS), is a diagnosis of exclusion made in cases in which there is clonal eosinophilia but an absence of genetic aberrations that define other disease subtypes. There is a need for further characterization of these cases in order to inform risk stratification and management. The importance of <i>JAK2</i> mutations in myeloproliferative neoplasms (MPN) as a whole is well established, although their role specifically in eosinophilic disorders is less clear, with only a minority of cases demonstrating <i>JAK2</i> abnormalities. Here, we report 2 cases with an exon 13 insertion-deletion (indel) mutation in <i>JAK2:</i> one with CEL-NOS and the second with an unspecified eosinophilic disorder. <i>JAK2</i> indels were not detected in a screen of suspected MPN cases (<i>n</i> = 592) without eosinophilia that tested negative for common MPN driver mutations. Our findings thus provide further evidence for a specific association between this rare mutation and clonal eosinophilic disorders.

scholarly journals JAK2 (and other genes) be nimble with MPN diagnosis, prognosis, and therapy

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Michele Ciboddo ◽  
Ann Mullally
Keyword(s):  
Clinical Decision Making ◽  
Phenotypic Diversity ◽  
Myeloproliferative Neoplasms ◽  
Clinical Decision ◽  
Prognostic Models ◽  
Driver Mutations ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
Substantial Progress ◽  
Made In

Abstract Now that the spectrum of somatic mutations that initiate, propagate, and drive the progression of myeloproliferative neoplasms (MPNs) has largely been defined, recent efforts have focused on integrating this information into clinical decision making. In this regard, the greatest progress has been made in myelofibrosis, in which high-molecular-risk mutations have been identified and incorporated into prognostic models to help guide treatment decisions. In this chapter, we focus on advances in 4 main areas: (1) What are the MPN phenotypic driver mutations? (2) What constitutes high molecular risk in MPN (focusing on ASXL1)? (3) How do we risk-stratify patients with MPN? And (4) What is the significance of molecular genetics for MPN treatment? Although substantial progress has been made, we still have an incomplete understanding of the molecular basis for phenotypic diversity in MPN, and few rationally designed therapeutic approaches to target high-risk mutations are available. Ongoing research efforts in these areas are critical to understanding the biological consequences of genetic heterogeneity in MPN and to improving outcomes for patients.

scholarly journals Clinical and biological characterization of MPN patients harboring two driver mutations, a French intergroup of myeloproliferative neoplasms (FIM) study

2018 ◽  
Vol 93 (4) ◽  
pp. E84-E86 ◽  
Author(s):  
Olivier Mansier ◽  
Damien Luque Paz ◽  
Jean-Christophe Ianotto ◽  
Yannick Le Bris ◽  
Aurélie Chauveau ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Driver Mutations ◽  
Biological Characterization

Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation

2020 ◽  
Vol 20 (7) ◽  
pp. 490-500 ◽  
Author(s):  
Justin S. Becker ◽  
Amir T. Fathi
Keyword(s):  
Genome Structure ◽  
Cellular Metabolism ◽  
Standard Of Care ◽  
Competitive Inhibitor ◽  
Driver Mutations ◽  
New Class ◽  
Regulatory Enzymes ◽  
Idh Mutations ◽  
Genomic Characterization

The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2- hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens.

Bioactivity of Marine Natural Product Xyloketals

2020 ◽  
Vol 17 ◽  
Author(s):  
Biswajit Panda ◽  
Amal Kumar Gooyee
Keyword(s):  
Natural Products ◽  
Marine Natural Product ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Activity Inhibition ◽  
Life Saving ◽  
Behavior Suppression ◽  
Major Emphasis ◽  
Made In

: Oceans can play a major role in supplying life-saving medicines in the world in future. Although considerable progress has been made in finding new medicines from marine sources, large efforts are still necessary to examine such molecules for clinical applications. Xyloketals are an important group of natural products with various powerful and prominent bioactivities such as inhibition of acetylcholine esterase, antioxidant activity, inhibition of L-calcium channels, radicalscavenging behavior, suppression of cell proliferation, reduction of neonatal hypoxic-ischemic brain injury, etc. This review describes the isolation and structural characterization of all xyloketal natural products giving major emphasis on their bioactivity.

Characterization of Auditory Disability and Its Relation to the Resilience

2018 ◽  
Vol 5 (2) ◽  
pp. 15
Author(s):  
Bibian Bibeca Bumbila García ◽  
Hernán Andrés Cedeño Cedeño ◽  
Tatiana Moreira Chica ◽  
Yaritza Rossana Parrales Ríos
Keyword(s):  
Social Integration ◽  
Conceptual Analysis ◽  
Disabled People ◽  
Disabled Students ◽  
Hearing Disability ◽  
Technical University ◽  
The Relationship ◽  
Made In

The objective of the work is to establish the characterization of the auditory disability and its relationship with resilience at the Technical University of Manabí. The article shows a conceptual analysis related to the inclusion and social integration of disabled students. Based on the fact that the person with disabilities grows and develops in the same way as that of people without disabilities and what usually happens is that disabled people are rejected and discriminated against based on a prefabricated and erroneous conceptualization of these people. The results associated with the application of the SV-RES test prepared by the researchers are shown (Saavedra & Villalta, 2008b). Characterization of the auditory deficit is made in the students, and the limitations that derive from it are pointed out. We analyze the particularities related to communication with students who have a hearing disability and resilience in this type of student, where some personal highlights that in this sense constitute an example of resilience. Finally, the results related to the study of the relationship between students' hearing disability and the level of resilience dimensions are shown.

scholarly journals Clonal approaches to understanding the impact of mutations on hematologic disease development

Blood ◽  
2019 ◽  
Vol 133 (13) ◽  
pp. 1436-1445 ◽  
Author(s):  
Jyoti Nangalia ◽  
Emily Mitchell ◽  
Anthony R. Green
Keyword(s):  
Somatic Mutations ◽  
Clonal Selection ◽  
Single Cells ◽  
Driver Mutations ◽  
Great Promise ◽  
Tumor Evolution ◽  
Disease Development ◽  
Hematopoietic Tissue ◽  
The Impact

Abstract Interrogation of hematopoietic tissue at the clonal level has a rich history spanning over 50 years, and has provided critical insights into both normal and malignant hematopoiesis. Characterization of chromosomes identified some of the first genetic links to cancer with the discovery of chromosomal translocations in association with many hematological neoplasms. The unique accessibility of hematopoietic tissue and the ability to clonally expand hematopoietic progenitors in vitro has provided fundamental insights into the cellular hierarchy of normal hematopoiesis, as well as the functional impact of driver mutations in disease. Transplantation assays in murine models have enabled cellular assessment of the functional consequences of somatic mutations in vivo. Most recently, next-generation sequencing–based assays have shown great promise in allowing multi-“omic” characterization of single cells. Here, we review how clonal approaches have advanced our understanding of disease development, focusing on the acquisition of somatic mutations, clonal selection, driver mutation cooperation, and tumor evolution.

scholarly journals Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine

2021 ◽  
Vol 7 (3) ◽  
pp. 47
Author(s):  
Marios Lange ◽  
Rodiola Begolli ◽  
Antonis Giakountis
Keyword(s):  
Disease Onset ◽  
Cancer Genome ◽  
Driver Mutations ◽  
Nucleotide Polymorphisms ◽  
Structural Variations ◽  
Coding Regions ◽  
Functional Variants ◽  
Coding Variants ◽  
Clinical Potential

The cancer genome is characterized by extensive variability, in the form of Single Nucleotide Polymorphisms (SNPs) or structural variations such as Copy Number Alterations (CNAs) across wider genomic areas. At the molecular level, most SNPs and/or CNAs reside in non-coding sequences, ultimately affecting the regulation of oncogenes and/or tumor-suppressors in a cancer-specific manner. Notably, inherited non-coding variants can predispose for cancer decades prior to disease onset. Furthermore, accumulation of additional non-coding driver mutations during progression of the disease, gives rise to genomic instability, acting as the driving force of neoplastic development and malignant evolution. Therefore, detection and characterization of such mutations can improve risk assessment for healthy carriers and expand the diagnostic and therapeutic toolbox for the patient. This review focuses on functional variants that reside in transcribed or not transcribed non-coding regions of the cancer genome and presents a collection of appropriate state-of-the-art methodologies to study them.

scholarly journals Drug delivery applications of poly-γ-glutamic acid

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olalekan A. Balogun-Agbaje ◽  
Olubusola A. Odeniyi ◽  
Michael A. Odeniyi
Keyword(s):  
Drug Delivery ◽  
Glutamic Acid ◽  
Site Characterization ◽  
Fermentation Medium ◽  
Production Optimization ◽  
Main Body ◽  
Crucial Step ◽  
Drug Delivery Application ◽  
Made In

Abstract Background Poly-γ-glutamic acid (γ-PGA) is a biopolymer of microbial origin, consisting of repeating units of l-glutamic acid and/or D-glutamic acid. The biopolymer has found use in the fields of agriculture, food, wastewater, and medicine, owing to its non-toxic, biodegradable, and biocompatible properties. Due to its biodegradability, γ-PGA is being tipped to dislodge synthetic plastics in drug delivery application. High cost of production, relative to plastics, is however a clog in the wheel of achieving this. Main body of abstract This review looked at the production, nanoparticles fabrication, and drug delivery application of γ-PGA. γ-PGA production optimization by modifying the fermentation medium to tailor towards the production of desirable polymer at reduced cost and techniques for the formulation of γ-PGA nanoparticle as well as its characterization were discussed. This review also evaluated the application of γ-PGA and its nanoparticles in the delivery of drugs to action site. Characterization of γ-PGA and its nanoparticles is a crucial step towards determining the applicability of the biopolymer. γ-PGA has been used in the delivery of active agents to action sites. Conclusion This review highlights some of the efforts that have been made in the appraisal of γ-PGA and its nanoparticles for drug delivery. γ-PGA is a candidate for future extensive use in drug delivery.

scholarly journals Paving the way for transgenic schistosomes

Parasitology ◽  
2011 ◽  
Vol 139 (5) ◽  
pp. 651-668 ◽  
Author(s):  
S. BECKMANN ◽  
C. G. GREVELDING
Keyword(s):  
Rna Interference ◽  
Initial Phase ◽  
Functional Characterization ◽  
Reporter Genes ◽  
Significant Progress ◽  
Gene Insertion ◽  
Remarkable Progress ◽  
Made In ◽  
Silence Gene

SUMMARYIn parasitological research, significant progress has been made with respect to genomics and transcriptomics but transgenic systems for functional gene analyses are mainly restricted to the protozoan field. Gene insertion and knockout strategies can be applied to parasitic protozoa as well as gene silencing by RNA interference (RNAi). By contrast, research on parasitic helminthes still lags behind. Along with the major advances in genome and transcriptome analyses e.g. for schistosomes, methods for the functional characterization of genes of interest are still in their initial phase and have to be elaborated now, at the beginning of the post-genomic era. In this review we will summarize attempts made in the last decade regarding the establishment of protocols to transiently and stably transform or transfect schistosomes. Besides approaches using particle bombardment, electroporation or virus-based infection strateies to introduce DNA constructs into adult and larval schistosome stages to express reporter genes, first approaches have also been made in establishing protocols based on soaking, lipofection, and/or electroporation for RNA interference to silence gene activity. Although in these cases remarkable progress can be seen, the schistosome community eagerly awaits major breakthroughs especially with respect to stable transformation, but also for silencing or knock-down strategies for every schistosome gene of interest.

scholarly journals Viruses and Virus Diseases of Rubus

Plant Disease ◽  
2013 ◽  
Vol 97 (2) ◽  
pp. 168-182 ◽  
Author(s):  
Robert R. Martin ◽  
Stuart MacFarlane ◽  
Sead Sabanadzovic ◽  
Diego Quito ◽  
Bindu Poudel ◽  
...  
Keyword(s):  
Far East ◽  
Fruit Production ◽  
Detection Methods ◽  
Center Of Origin ◽  
The Family ◽  
Production Stages ◽  
Rubus Species ◽  
Polymerase Chain ◽  
Made In

Blackberry and raspberry are members of the family Rosaceae. They are classified in the genus Rubus, which comprises hundreds of species and has a center of origin in the Far East. Rubus is divided into 15 subgenera with blackberries classified in the Rubus (formerly Eubatus) and raspberries in the Idaeobatus subgenera. Rubus species are propagated vegetatively and are subject to infection by viruses during development, propagation, and fruit production stages. Reports of initial detection and symptoms of more than 30 viruses, virus-like diseases, and phytoplasmas affecting Rubus spp. were reviewed more than 20 years ago. Since the last review on Rubus viruses, significant progress has been made in the molecular characterization of many of the viruses that infect Rubus spp. Currently, reverse transcription–polymerase chain reaction detection methods are available for most of the viruses known to infect Rubus. The goals of this article are to update the knowledge on previously characterized viruses of Rubus, highlight recently described viruses, review the virus-induced symptoms, describe the advances made in their detection, and discuss our knowledge about several virus complexes that cause serious diseases in Rubus. Virus complexes have been identified recently as the major cause of diseases in blackberries and raspberries.

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