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The Western Journal of Medicine Aug 1977A study was done with 27 patients who met the following criteria: (1) anemia, (2) cellular bone marrow not diagnostic of leukemia, (3) absence of underlying disease that...
A study was done with 27 patients who met the following criteria: (1) anemia, (2) cellular bone marrow not diagnostic of leukemia, (3) absence of underlying disease that could account for the hematologic abnormalities at time of initial study and (4) absence of iron, B(12) or folate deficiency. Of the 27 patients, 13 had ringed sideroblasts and 14 did not. Eleven patients received corticosteroids, 18 received folate, 23 pyridoxine and 12 androgens. Two partial responses occurred in the sideroblastic group and were attributed to androgen therapy in one patient and pyridoxine therapy in the other. In the nonsideroblastic group, two partial responses occurred which were attributed to prednisone therapy. Transfusions were required in 23 patients. Leukemia developed in six patients. It is concluded that currently used treatments have little effect on refractory anemia and that in most patients continuing transfusions are required. In a small percentage of patients, there is transformation to leukemia.
Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Sideroblastic; Child; Female; Humans; Male; Middle Aged
PubMed: 898952
DOI: No ID Found -
Journal of Personalized Medicine Jun 2024The ATP-binding cassette (ABC) transporters are a vast group of 48 membrane proteins, some of which are of notable physiological and clinical importance. Some ABC... (Review)
Review
The ATP-binding cassette (ABC) transporters are a vast group of 48 membrane proteins, some of which are of notable physiological and clinical importance. Some ABC transporters are involved in functions such as the transport of chloride ions, bilirubin, reproductive hormones, cholesterol, and iron. Consequently, genetic or physiological disruption in these functions is manifested in various disease processes like cystic fibrosis, Tangier disease, and sideroblastic anemia. Among other etiologies, primary sideroblastic anemia results from a genetic mutation in the ATP-binding cassette-7 (ABCB7), a member of the ABC transporter family. There are not many articles specifically tackling the disease processes caused by ABC transporters in detail. Some testing methodologies previously reported in the available literature for investigating sideroblastic anemia need updating. Here, we expound on the relevance of ABCB7 as a clinically important ABC transporter and a rare participant in the disease process of Sideroblastic anemia. The other genetic and secondary etiologies of sideroblastic anemia, which do not involve mutations in the ABCB7 protein, are also described. We review the pathophysiology, clinical course, symptoms, diagnosis, and treatment of sideroblastic anemia with a focus on modern technologies for laboratory testing.
PubMed: 38929857
DOI: 10.3390/jpm14060636 -
Haematologica Nov 2013
Topics: Acetamides; Adult; Aged; Anemia, Sideroblastic; Anti-Infective Agents; Bone Marrow Cells; Cohort Studies; Female; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Retrospective Studies
PubMed: 24186315
DOI: 10.3324/haematol.2013.092395 -
Biophysics Reports Apr 2021As a cofactor, iron-sulfur (Fe-S) cluster binds to proteins or enzymes that play important roles in various important biological processes, including DNA synthesis and...
As a cofactor, iron-sulfur (Fe-S) cluster binds to proteins or enzymes that play important roles in various important biological processes, including DNA synthesis and repair, mitochondrial function, gene transcription and translation. In mammals, the core components involved in Fe-S cluster biosynthesis are considered to include the scaffold protein ISCU, cysteine desulfurase NFS1 and its accessory proteins ISD11 and ACP, and frataxin (FXN). Proteins involved in Fe-S cluster transfer have been found to include HSC20/HSPA9, as chaperone system, and Fe-S cluster carriers. The biosynthesis and transfer of Fe-S clusters to Fe-S recipients require fine-tune regulation. Recently, significant progress has been made in the structure and mechanism of mitochondrial Fe-S biosynthesis and transfer. Based on, especially, the development of DNA sequencing technology, bioinformatics, and gene editing technology, diseases caused by mutations of Fe-S cluster-related genes have been revealed in recent years, promoting the rapid development in the field of Fe-S and human health. This review focuses on the function of genes involved in Fe-S cluster biosynthesis and transfer and on the diseases caused by the mutations of the related genes. Finally, some questions we are facing are raised, new hypotheses presented, and the perspectives discussed.
PubMed: 37288145
DOI: 10.52601/bpr.2021.200038 -
Oncology (Williston Park, N.Y.) Jan 2007Most adult patients with hematopoietic failure due to myelodysplastic syndrome (MDS) are treated with supportive care measures, including hematopoietic growth factors... (Review)
Review
Most adult patients with hematopoietic failure due to myelodysplastic syndrome (MDS) are treated with supportive care measures, including hematopoietic growth factors (epoetin alfa, darbepoetin alfa, filgrastim, pegfilgrastim, sargramostim), red blood cell or platelet transfusions, and antimicrobial agents. Allogeneic stem cell transplantation can be curative, but only a small subset of patients are eligible for transplantation, and until recently there were few options other than supportive care for transplant-ineligible patients. Since 2004, the US Food and Drug Administration (FDA) has approved three new therapies specifically for the indication of MDS: two DNA methyltransferase inhibitors (azacitidine and decitabine) and an immunomodulatory agent (lenalidomide). Several other drugs are used by clinicians for treatment of patients with MDS, but are not specifically FDA-approved for this indication. With several therapeutic options available, yet none of them effective in the majority of cases, it can be challenging for clinicians to choose the most appropriate treatment for an individual patient. Here we discuss a risk-based management approach to MDS that incorporates recent data regarding these new therapies. While many questions remain about the optimal use of newer agents, the long-standing perception of MDS as a syndrome where therapeutic nihilism is the only realistic approach is slowly beginning to change.
Topics: Anemia, Sideroblastic; Antilymphocyte Serum; Azacitidine; Benzoates; DNA Modification Methylases; Decitabine; Deferasirox; Enzyme Inhibitors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Histone Deacetylase Inhibitors; Humans; Immunosuppressive Agents; Interleukin-11; Iron Chelating Agents; Lenalidomide; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Prognosis; Risk; Stem Cell Transplantation; Thalidomide; Triazoles
PubMed: 17313156
DOI: No ID Found -
British Journal of Haematology Oct 2008Sideroblastic anaemia includes a heterogeneous group of rare conditions, characterized by decreased haem synthesis and mitochondrial iron overload, which are diagnosed... (Review)
Review
Sideroblastic anaemia includes a heterogeneous group of rare conditions, characterized by decreased haem synthesis and mitochondrial iron overload, which are diagnosed by the presence of ringed sideroblasts in the bone marrow aspirate. The most frequent form is X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of haem synthesis in erythroid precursors and is post-transcriptionally controlled by the iron regulatory proteins. Impaired haem production causes variable degrees of anaemia and mitochondrial iron accumulation as ringed sideroblasts. The heterogeneity and complexity of sideroblastic anaemia is explained by an increasing number of recognized molecular defects. New forms have been recognized as being linked to the deficient function of mitochondrial proteins involved in iron-sulphur cluster biogenesis, such as ABCB7 and GLRX5, which are extremely rare but represent important biological models. Local mitochondrial iron overload is present in all sideroblastic anaemias, whereas systemic iron overload occurs only in the forms because of primary or secondary deficiency of ALAS2.
Topics: 5-Aminolevulinate Synthetase; Anemia, Sideroblastic; Animals; Chromosomes, Human, X; Humans; Models, Animal; Mutation; Pyridoxine; Vitamin B Complex
PubMed: 18637800
DOI: 10.1111/j.1365-2141.2008.07290.x -
Experimental Hematology May 2017Sideroblastic anemia is characterized by the presence of ring sideroblasts (RSs), which are caused by iron accumulation in the mitochondria of erythroblasts and are...
Sideroblastic anemia is characterized by the presence of ring sideroblasts (RSs), which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both the acquired and congenital forms of the disease. However, the mechanism leading to RS formation remains elusive. Acquired sideroblastic anemia is usually observed in myelodysplastic syndrome (MDS). Because a subset of MDS harbors a somatic mutation of TET2, it may be involved in iron metabolism and/or heme biosynthesis in erythroblasts. Tet2 knockdown (Tet2) induced exhibited mild normocytic anemia and elevated serum ferritin levels in 4-month-old mice. Although typical RSs were not observed, increased mitochondrial ferritin (FTMT) amounts were observed in the erythroblasts of Tet2-knockdown mice. Quantitative real-time polymerase chain reaction demonstrated significant dysregulation of genes involved in iron and heme metabolism, including Hmox1, Fech, Abcb7, and Sf3b1 downregulation. After the identification of a cytosine-guanine island in the promoters of Fech, Abcb7, and Sf3b1, we evaluated DNA methylation status and found significantly higher methylation levels at the CpG sites in the erythroblasts of Tet2-knockdown mice. Furthermore, Tet2 knockdown in erythroblasts resulted in decreased heme concentration and accumulation of FTMT. Therefore, TET2 plays a role in the iron and heme metabolism in erythroblasts.
Topics: ATP-Binding Cassette Transporters; Anemia; Animals; DNA Methylation; DNA-Binding Proteins; Dioxygenases; Erythroblasts; Heme; Heme Oxygenase-1; Iron; Membrane Proteins; Mice; Mice, Knockout; Phosphoproteins; Proto-Oncogene Proteins; RNA Splicing Factors; Real-Time Polymerase Chain Reaction
PubMed: 28167288
DOI: 10.1016/j.exphem.2017.01.002 -
American Journal of Hematology Mar 2017Ring 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), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).
DIAGNOSIS
MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). MDS/MPN-RS-T, now a formal entity in the MDS/MPN overlap syndromes, has diagnostic features of MDS-RS-SLD, along with a platelet count ≥ 450 × 10(9)/L and large atypical megakaryocytes (similar to BCR-ABL1 negative MPN).
MUTATIONS AND KARYOTYPE
Mutations in SF3B1 are seen in ≥80% of patients with MDS-RS-SLD and MDS/MPN-RS-T, and strongly correlate with the presence of BM RS; MDS/MPN-RS-T patients also demonstrate JAK2V617F, ASXL1, DNMT3A, SETBP1, and TET2 mutations; with ASXL1/SETBP1 mutations adversely impacting survival. Cytogenetic abnormalities are uncommon in both diseases.
RISK STRATIFICATION
Most patients with MDS-RS-SLD are stratified into lower risk groups by the revised-International Prognostic Scoring System (R-IPSS). Disease outcome in MDS/MPN-RS-T is better than that of MDS-RS-SLD, but worse than that of essential thrombocythemia. Both diseases have a low risk of leukemic TREATMENT: Anemia and iron overload are complications seen in both and are managed similar to lower risk MDS and MPN. Aspirin therapy is reasonable in MDS/MPN-RS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs is uncertain.
Topics: Anemia, Refractory; Anemia, Sideroblastic; Humans; Mutation; Myelodysplastic Syndromes; Risk Assessment; Thrombocytosis
PubMed: 28188970
DOI: 10.1002/ajh.24637 -
Clinical Case Reports Sep 2020Hypocupremia due to zinc products can cause sideroblastic anemia and neutropenia and mimics other serious hematological disorders. Early consideration of the copper...
Hypocupremia due to zinc products can cause sideroblastic anemia and neutropenia and mimics other serious hematological disorders. Early consideration of the copper deficiency and a thorough clinical history can prevent unnecessary interventions.
PubMed: 32983473
DOI: 10.1002/ccr3.2987 -
Biochemistry Jun 2010Iron-sulfur (Fe-S) proteins contain prosthetic groups consisting of two or more iron atoms bridged by sulfur ligands, which facilitate multiple functions, including... (Review)
Review
Iron-sulfur (Fe-S) proteins contain prosthetic groups consisting of two or more iron atoms bridged by sulfur ligands, which facilitate multiple functions, including redox activity, enzymatic function, and maintenance of structural integrity. More than 20 proteins are involved in the biosynthesis of iron-sulfur clusters in eukaryotes. Defective Fe-S cluster synthesis not only affects activities of many iron-sulfur enzymes, such as aconitase and succinate dehydrogenase, but also alters the regulation of cellular iron homeostasis, causing both mitochondrial iron overload and cytosolic iron deficiency. In this work, we review human Fe-S cluster biogenesis and human diseases that are caused by defective Fe-S cluster biogenesis. Fe-S cluster biogenesis takes place essentially in every tissue of humans, and products of human disease genes, including frataxin, GLRX5, ISCU, and ABCB7, have important roles in the process. However, the human diseases, Friedreich ataxia, glutaredoxin 5-deficient sideroblastic anemia, ISCU myopathy, and ABCB7 sideroblastic anemia/ataxia syndrome, affect specific tissues, while sparing others. Here we discuss the phenotypes caused by mutations in these different disease genes, and we compare the underlying pathophysiology and discuss the possible explanations for tissue-specific pathology in these diseases caused by defective Fe-S cluster biogenesis.
Topics: ATP-Binding Cassette Transporters; Anemia, Sideroblastic; Animals; Cerebellar Ataxia; Friedreich Ataxia; Glutaredoxins; Homeostasis; Humans; Iron; Iron-Binding Proteins; Iron-Sulfur Proteins; Mitochondrial Myopathies; Mutation; Syndrome; Frataxin
PubMed: 20481466
DOI: 10.1021/bi1004798