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Blood Mar 2022
Topics: Anemia, Sideroblastic; Erythroid Precursor Cells; Humans; RNA
PubMed: 35357481
DOI: 10.1182/blood.2021014923 -
International Journal of Molecular... Sep 2021Vertebrates generate mature red blood cells (RBCs) via a highly regulated, multistep process called erythropoiesis. Erythropoiesis involves synthesis of heme and... (Review)
Review
Vertebrates generate mature red blood cells (RBCs) via a highly regulated, multistep process called erythropoiesis. Erythropoiesis involves synthesis of heme and hemoglobin, clearance of the nuclei and other organelles, and remodeling of the plasma membrane, and these processes are exquisitely coordinated by specific regulatory factors including transcriptional factors and signaling molecules. Defects in erythropoiesis can lead to blood disorders such as congenital dyserythropoietic anemias, Diamond-Blackfan anemias, sideroblastic anemias, myelodysplastic syndrome, and porphyria. The molecular mechanisms of erythropoiesis are highly conserved between fish and mammals, and the zebrafish () has provided a powerful genetic model for studying erythropoiesis. Studies in zebrafish have yielded important insights into RBC development and established a number of models for human blood diseases. Here, we focus on latest discoveries of the molecular processes and mechanisms regulating zebrafish erythropoiesis and summarize newly established zebrafish models of human anemias.
Topics: Anemia, Aplastic; Animals; Disease Models, Animal; Embryonic Development; Erythrocytes; Erythropoiesis; Humans; Zebrafish
PubMed: 34638816
DOI: 10.3390/ijms221910475 -
Advanced Biomedical Research 2014Helicobacter pylori has been associated with colonization of gastro duodenal mucosa of humans from millions of years. The main burden of the disese is in the developing... (Review)
Review
Helicobacter pylori has been associated with colonization of gastro duodenal mucosa of humans from millions of years. The main burden of the disese is in the developing countries, due to overcrowding and poor hygiene. If left untreated it leads to lot of sequlae from minor to sinister diseases over a period of time. The main challenges that remain are prevention of H. pylori-related diseases by effective treatment and screening procedures and development of a vaccine, which can address all these issues including beneficial aspects of H. pylori. The literature pertaining to different aspects of H. pylori were scrutinized from Pubmed. Material on clinical behavior, complications of chronic gastric involvement, and prevention besides role of H. pylori in nongastric diseases and the latest trends of management was collected for research and review. We continue to face many challenges. The prevention of cancer of the stomach, a worst sequlae of H. pylori continues to be a big challenge despite population screening and prevention surveys being underway in many countries. On the other hand continued scientific work has now unfolded involvement of H. pylori in extragastric diseases like cerebrovascular, cardiovascular, idiopathic thrombocytopenia, sideroblastic anemia, mental diseases, and collagen vascular diseases. In contrast, the beneficial effects of H. pylori with respect to allergic diseases and obesity are now clear. Moreover, problem of drug resistance for eradication of H. pylori has arisen for which novel treatments are being tried. Lactobacillus reuteri having anti H. pylori action is emerging as one of the promising treatment.
PubMed: 24627871
DOI: 10.4103/2277-9175.125844 -
International Journal of Molecular... May 2020tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs,... (Review)
Review
tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation. It was recently discovered that partial loss-of-function mutations in TRNT1 are associated with various, seemingly unrelated human diseases including sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD), retinitis pigmentosa with erythrocyte microcytosis, and progressive B-cell immunodeficiency. In addition, even within the same disease, the severity and range of the symptoms vary greatly, suggesting a broad, pleiotropic impact of imparting TRNT1 function on diverse cellular systems. Here, we describe the current state of knowledge of the TRNT1 function and the phenotypes associated with mutations in .
Topics: Adenosine; Animals; Cytosine; Disease; Humans; Mitochondria; Nucleotidyltransferases; RNA, Transfer
PubMed: 32471101
DOI: 10.3390/ijms21113780 -
Pediatric Blood & Cancer May 2017Symptomatic β-thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses...
Symptomatic β-thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses are typically sufficient to diagnose the disease, sometimes the diagnosis can be more challenging. We describe a series of patients with β-thalassemia whose diagnosis was delayed, required bone marrow examination in one affected member of each family, and revealed ringed sideroblasts, highlighting the association of this morphological finding with these disorders. Thus, in the absence of characteristic congenital sideroblastic mutations or causes of acquired sideroblastic anemia, the presence of ringed sideroblasts should raise the suspicion of β-thalassemia.
Topics: Adolescent; Adult; Anemia, Sideroblastic; Bone Marrow Cells; Bone Marrow Examination; Child; Erythroblasts; Erythrocytes, Abnormal; Female; Hematologic Diseases; Humans; Infant; Male; beta-Thalassemia
PubMed: 27808451
DOI: 10.1002/pbc.26324 -
Tidsskrift For Den Norske Laegeforening... Nov 2017
Topics: Aged; Anemia, Refractory; Anemia, Sideroblastic; Humans; Iron; Male; Staining and Labeling
PubMed: 29135187
DOI: 10.4045/tidsskr.17.0502 -
Annales de Biologie Clinique 2013Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included... (Review)
Review
Myelodysplastic syndromes (MDS) are myeloid disorders with various clinical and biological presentations. The French-American-British (FAB-1982) classification included five categories basing on morphology and bone marrow blast count. Three criteria are taken into account: 1) the percentage of blasts in peripheral blood and bone marrow, 2) the percentage of ringed sideroblasts, and 3) the number of monocytes in peripheral blood. The World Health Organization classification (WHO 2001, 2008) modifies the FAB system by also taking cytogenetic characteristics and molecular biology into consideration. The last classification (WHO-2008) takes into account: 1) the number of peripheral cytopenia, 2) the percentage of blasts in peripheral blood and bone marrow, 3) the percentage of ringed sideroblasts, 4) the possible presence of Auer Rods, and 5) the detection of a cytogenetic abnormality (the isolated 5q deletion). The following subgroups are defined: refractory cytopenia with unilineage dysplasia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts, myelodysplastic syndrome unclassifiable and myelodysplastic syndrome with isolated del(5q).
Topics: Americas; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; France; Humans; Janus Kinase 2; Myelodysplastic Syndromes; Myeloproliferative Disorders; United Kingdom; World Health Organization
PubMed: 23587576
DOI: 10.1684/abc.2013.0804 -
Human Mutation Nov 2021The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders of erythropoiesis characterized by pathologic deposits of iron in the... (Review)
Review
The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders of erythropoiesis characterized by pathologic deposits of iron in the mitochondria of developing erythroblasts. Mutations in the mitochondrial glycine carrier SLC25A38 cause the most common recessive form of CSA. Nonetheless, the disease is still rare, there being fewer than 70 reported families. Here we describe the clinical phenotype and genotypes of 31 individuals from 24 families, including 11 novel mutations. We also review the spectrum of reported mutations and genotypes associated with the disease, describe the unique localization of missense mutations in transmembrane domains and account for the presence of several alleles in different populations.
Topics: Anemia, Sideroblastic; Child, Preschool; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Mitochondrial Membrane Transport Proteins; Mutation; Phenotype
PubMed: 34298585
DOI: 10.1002/humu.24267 -
American Journal of Hematology Jun 2015Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include... (Review)
Review
DISEASE OVERVIEW
Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T).
DIAGNOSIS
RARS is a lower risk myelodysplastic syndrome (MDS) with dysplasia limited to the erythroid lineage, <5% bone marrow (BM) blasts and ≥15% BM RS. RARS-T is a provisional entity in the MDS/MPN (myeloproliferative neoplasm) overlap syndromes, with diagnostic features of RARS, along with a platelet count ≥450 × 10(9)/L and large atypical megakaryocytes similar to those observed in BCR-ABL1 negative MPN. Mutations and Karyotype: Mutations in the SF3B1 gene are seen in ≥80% of patients with RARS and RARS-T, and strongly correlate with the presence of BM RS; RARS-T patients have additional mutations such as, JAK2V617F (∼60%), MPL (<5%), and CALR (<5%). Cytogenetic abnormalities are uncommon in both RARS and RARS-T.
RISK STRATIFICATION
Most patients with RARS are stratified into lower risk groups by the International Prognostic Scoring System (IPSS) for MDS and the revised IPSS. Disease outcome in RARS-T is better than that of RARS, but worse than that of essential thrombocytosis. Both RARS and RARS-T have a low risk of leukemic transformation.
TREATMENT
Anemia and iron overload are complications in both diseases and are managed similar to lower risk MDS. Aspirin therapy is reasonable in RARS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs is uncertain. Case reports of RARS-T therapy with lenalidomide warrant additional studies.
Topics: Anemia, Refractory; Anemia, Sideroblastic; Angiogenesis Inhibitors; Aspirin; Female; Humans; Iron Overload; Janus Kinase 2; Lenalidomide; Male; Mutation; Myelodysplastic Syndromes; Phosphoproteins; Platelet Aggregation Inhibitors; RNA Splicing Factors; Receptors, Thrombopoietin; Ribonucleoprotein, U2 Small Nuclear; Risk Factors; Thalidomide; Thrombocytosis
PubMed: 25899435
DOI: 10.1002/ajh.24038