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British Journal of Haematology Nov 2020Since the inception of the British Society for Haematology (BSH) 60 years ago, our increased scientific understanding of iron metabolism, together with clinical... (Review)
Review
Since the inception of the British Society for Haematology (BSH) 60 years ago, our increased scientific understanding of iron metabolism, together with clinical developments, have changed the way we diagnose and treat its disorders. In the UK, perhaps the most notable contributions relate to iron overload, some of which I will outline from personal experience. Diagnostically, this began with the identification of serum ferritin as a marker of iron overload and continued later with the application of MRI-based imaging techniques for iron and its distribution. Therapeutically, the first trials of both parenteral and oral chelation, which have radically changed the outcomes of transfusional iron-overloaded patients, took place in the UK and are now part of standard clinical practice. During this time, our scientific understanding of iron metabolism at a cellular and systemic level have advanced the diagnosis and treatment of inherited disorders of iron metabolism. There are potential novel applications related to our recent understanding of hepcidin metabolism and manipulation.
Topics: Biomarkers; Disease Management; Disease Susceptibility; Hematologic Diseases; Hemochromatosis; Humans; Iron; Iron Chelating Agents; Iron Overload
PubMed: 33190267
DOI: 10.1111/bjh.17164 -
Biomolecules Jun 2022Microvesicles or ectosomes represent a major type of extracellular vesicles that are formed by outward budding of the plasma membrane. Typically, they are bigger than... (Review)
Review
Microvesicles or ectosomes represent a major type of extracellular vesicles that are formed by outward budding of the plasma membrane. Typically, they are bigger than exosomes but smaller than apoptotic vesicles, although they may overlap with both in size and content. Their release by cells is a means to dispose redundant, damaged, or dangerous material; to repair membrane lesions; and, primarily, to mediate intercellular communication. By participating in these vital activities, microvesicles may impact a wide array of cell processes and, consequently, changes in their concentration or components have been associated with several pathologies. Of note, microvesicles released by leukocytes, red blood cells, and platelets, which constitute the vast majority of plasma microvesicles, change under a plethora of diseases affecting not only the hematological, but also the nervous, cardiovascular, and urinary systems, among others. In fact, there is evidence that microvesicles released by blood cells are significant contributors towards pathophysiological states, having inflammatory and/or coagulation and/or immunomodulatory arms, by either promoting or inhibiting the relative disease phenotypes. Consequently, even though microvesicles are typically considered to have adverse links with disease prognosis, progression, or outcomes, not infrequently, they exert protective roles in the affected cells. Based on these functional relations, microvesicles might represent promising disease biomarkers with diagnostic, monitoring, and therapeutic applications, equally to the more thoroughly studied exosomes. In the current review, we provide a summary of the features of microvesicles released by blood cells and their potential implication in hematological and non-hematological diseases.
Topics: Blood Platelets; Cell-Derived Microparticles; Exosomes; Extracellular Vesicles; Hematologic Diseases; Humans
PubMed: 35740926
DOI: 10.3390/biom12060803 -
Acta Obstetricia Et Gynecologica... May 2019Clinicians should provide fertility counseling to all patients receiving gonadotoxic treatment. International scientific societies have mainly focused on oncological... (Review)
Review
Clinicians should provide fertility counseling to all patients receiving gonadotoxic treatment. International scientific societies have mainly focused on oncological patients, and fewer efforts have been made to apply these recommendations to women diagnosed with benign disease (eg benign hematological diseases, autoimmune diseases, and gynecological or genetic disorders). However, these indications account for 8%-13% of the demand for fertility preservation. The risk of premature ovarian failure due to treatment, or to the disease itself, can be considered fairly high for many young women. Counseling and adequate management of these women require particular attention due to the severe health conditions that are associated with some of these diseases. In this review, we address specific issues related to providing adequate fertility counseling and management for women who have been diagnosed with the major non-oncological indications, based on the literature and on our clinical experience.
Topics: Autoimmune Diseases; Counseling; Female; Fertility Preservation; Genetic Diseases, Inborn; Genital Diseases, Female; Hematologic Diseases; Humans; Infertility, Female; Medication Therapy Management
PubMed: 30771251
DOI: 10.1111/aogs.13577 -
EMBO Molecular Medicine Aug 2019Hematopoiesis, or the process of blood cell production, is a paradigm of multi-lineage cellular differentiation that has been extensively studied, yet in many aspects... (Review)
Review
Hematopoiesis, or the process of blood cell production, is a paradigm of multi-lineage cellular differentiation that has been extensively studied, yet in many aspects remains incompletely understood. Nearly all clinically measured hematopoietic traits exhibit extensive variation and are highly heritable, underscoring the importance of genetic variation in these processes. This review explores how human genetics have illuminated our understanding of hematopoiesis in health and disease. The study of rare mutations in blood and immune disorders has elucidated novel roles for regulators of hematopoiesis and uncovered numerous important molecular pathways, as seen through examples such as Diamond-Blackfan anemia and the GATA2 deficiency syndromes. Additionally, population studies of common genetic variation have revealed mechanisms by which human hematopoiesis can be modulated. We discuss advances in functionally characterizing common variants associated with blood cell traits and discuss therapeutic insights, such as the discovery of BCL11A as a modulator of fetal hemoglobin expression. Finally, as genetic techniques continue to evolve, we discuss the prospects, challenges, and unanswered questions that lie ahead in this burgeoning field.
Topics: Animals; Genetic Predisposition to Disease; Genome-Wide Association Study; Hematologic Diseases; Hematopoiesis; Humans; Mutation; Phenotype
PubMed: 31313878
DOI: 10.15252/emmm.201910316 -
Blood disease-causing and -suppressing transcriptional enhancers: general principles and mechanisms.Blood Advances Jul 2019Intensive scrutiny of human genomes has unveiled considerable genetic variation in coding and noncoding regions. In cancers, including those of the hematopoietic system,... (Review)
Review
Intensive scrutiny of human genomes has unveiled considerable genetic variation in coding and noncoding regions. In cancers, including those of the hematopoietic system, genomic instability amplifies the complexity and functional consequences of variation. Although elucidating how variation impacts the protein-coding sequence is highly tractable, deciphering the functional consequences of variation in noncoding regions (genome reading), including potential transcriptional-regulatory sequences, remains challenging. A crux of this problem is the sheer abundance of gene-regulatory sequence motifs ( elements) mediating protein-DNA interactions that are intermixed in the genome with thousands of look-alike sequences lacking the capacity to mediate functional interactions with proteins in vivo. Furthermore, transcriptional enhancers harbor clustered elements, and how altering a single element within a cluster impacts enhancer function is unpredictable. Strategies to discover functional enhancers have been innovated, and human genetics can provide vital clues to achieve this goal. Germline or acquired mutations in functionally critical (essential) enhancers, for example at the locus encoding a master regulator of hematopoiesis, have been linked to human pathologies. Given the human interindividual genetic variation and complex genetic landscapes of hematologic malignancies, enhancer corruption, creation, and expropriation by new genes may not be exceedingly rare mechanisms underlying disease predisposition and etiology. Paradigms arising from dissecting essential enhancer mechanisms can guide genome-reading strategies to advance fundamental knowledge and precision medicine applications. In this review, we provide our perspective of general principles governing the function of blood disease-linked enhancers and -centric mechanisms.
Topics: Animals; Blood Cells; Disease Susceptibility; Enhancer Elements, Genetic; GATA2 Transcription Factor; Gene Expression Regulation; Hematologic Diseases; Hematopoiesis; Humans; Models, Biological; Organ Specificity; Transcriptome
PubMed: 31289032
DOI: 10.1182/bloodadvances.2019000378 -
Medicina (Kaunas, Lithuania) Jul 2019Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD... (Review)
Review
Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.
Topics: Anemia; Celiac Disease; Hematologic Diseases; Humans; IgA Deficiency; Lymphoma
PubMed: 31311098
DOI: 10.3390/medicina55070373 -
The Pan African Medical Journal 2018
Topics: Adolescent; Child; Child, Preschool; Erythrocytes, Abnormal; Female; Hematologic Diseases; Hematologic Neoplasms; Humans; Infant; Male; Retrospective Studies; Vitamin B 12 Deficiency
PubMed: 30923599
DOI: 10.11604/pamj.2018.31.54.15498 -
International Journal of Hematology Jul 2016The use of precise, rationally designed gene-editing nucleases allows for targeted genome and transcriptome modification, and at present, four major classes of nucleases... (Review)
Review
The use of precise, rationally designed gene-editing nucleases allows for targeted genome and transcriptome modification, and at present, four major classes of nucleases are being employed: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. Each reagent shares the ability to recognize and bind a target sequence of DNA. Depending on the properties of the reagent, the DNA can be cleaved on one or both strands, or epigenetic changes can be mediated. These novel properties can impact hematological disease by allowing for: (1) direct modification of hematopoietic stem/progenitor cells (HSPCs), (2) gene alteration of hematopoietic lineage committed terminal effectors, (3) genome engineering in non-hematopoietic cells with reprogramming to a hematopoietic phenotype, and (4) transcriptome modulation for gene regulation, modeling, and discovery.
Topics: Endonucleases; Gene Editing; Gene Targeting; Genetic Therapy; Hematologic Diseases; Humans
PubMed: 27233509
DOI: 10.1007/s12185-016-2017-z -
International Journal of Molecular... Nov 2023Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and... (Review)
Review
Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has emerged as a promising adjunct in hematological diagnostics. This review delves into the transformative role of IR spectroscopy and highlights its applications in detecting and diagnosing various blood-related ailments. We discuss groundbreaking research findings and real-world applications while providing a balanced view of the potential and limitations of the technique. By integrating advanced technology with clinical needs, we offer insights into how IR spectroscopy may herald a new era of hematological disease diagnosis.
Topics: Humans; Spectroscopy, Fourier Transform Infrared; Spectrophotometry, Infrared; Hematology; Hematologic Diseases
PubMed: 38069330
DOI: 10.3390/ijms242317007 -
Biochimica Et Biophysica Acta Oct 1999The idiopathic Tn-syndrome, formerly called 'permanent mixed-field polyagglutinability', is a rare hematological disorder characterized by the expression of the... (Review)
Review
The idiopathic Tn-syndrome, formerly called 'permanent mixed-field polyagglutinability', is a rare hematological disorder characterized by the expression of the Tn-antigen on all blood cell lineages. The immunodominant epitope of the Tn-antigen is terminal alpha-N-acetylgalactosamine, O-glycosidically linked to protein. Normally this residue is 3'-substituted by 5-galactose thereby forming the core 1 structure known as the Thomsen-Friedenreich (TF) antigen (Galbeta1 ==> 3GalNAcalpha1 ==> Thr/Ser). The cause of the exposure of the Tn-antigen appears to be due to the silencing of the gene expression of beta1,3galactosyltransferase, since treatment of deficient Tn(+) lymphocyte T clones with 5'azacytidine or Na butyrate leads to reexpression of enzyme activity and the sialylated TF-antigen. The Tn-syndrome is acquired and permanent and affects both sexes at any age. Its origin is unknown. Pluripotent stem cells are affected since all lineages are involved but each one to a variable extent. Therefore, normal cells co-exist with Tn-transformed cells. Clinically, patients suffering from the Tn-syndrome appear healthy. Laboratory findings usually reveal moderate thrombocyto- and leukopenia and some signs of hemolytic anemia not warranting any treatment.
Topics: Anemia, Hemolytic; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Azacitidine; Blood Cells; Erythrocyte Membrane; Galactosyltransferases; Hematologic Diseases; Humans; Lectins; Leukopenia; Molecular Structure; Syndrome; Thrombocytopenia
PubMed: 10571017
DOI: 10.1016/s0925-4439(99)00069-1