Sideroblastic anemias in adults are often quickly labeled as myelodysplasias. We report two unfrequent observations of secondary acquired forms. The first one is a 15-year-old girl presented with severe cytopenias. The myelogram revealed the presence of vacuolated myeloid and erythroblastic precursors, with ring sideroblasts. Copper deficiency has been demonstrated in front of the association with collapsed cupremia and ceruleoplasminemia, with normal cupruria. The second case is a 70-year-old man, treated for 1 month with several lines of antibiotics for a skin infection, referred for cytopenias. The myelogram found vacuolated erythroblastic precursors and ring sideroblasts. Linezolid's responsibility has been proposed, with a favorable development after treatment has been stopped. These two observations, which describe unfrequent sideroblastic anemias, point out that this discovery should not lead to the diagnosis of myelodysplasia before having considered the many other etiologies.
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http://dx.doi.org/10.1684/abc.2021.1618 | DOI Listing |
Int J Mol Sci
December 2024
Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70125 Bari, Italy.
Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress.
View Article and Find Full Text PDFBlood
January 2025
Department of Pediatrics, Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA.
X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2024
Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Besides transfusion therapy, ineffective erythropoiesis contributes to systemic iron overload in myelodysplastic syndromes with ring sideroblasts (MDS-RS) via erythroferrone-induced suppression of hepcidin synthesis in the liver, leading to increased intestinal iron absorption. The underlying pathophysiology of MDS-RS, characterized by disturbed heme synthesis and mitochondrial iron accumulation, is less well understood. Several lines of evidence indicate that the mitochondrial transporter ABCB7 is critically involved.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Broad Institute of MIT and Harvard, Cambridge, Massachusets, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:
Protein lipoylation, a vital lysine post-translational modification, plays a crucial role in the function of key mitochondrial tricarboxylic acid cycle enzymatic complexes. In eukaryotes, lipoyl post-translational modification synthesis occurs exclusively through de novo pathways, relying on lipoyl synthesis/transfer enzymes, dependent upon mitochondrial fatty acid and Fe-S cluster biosynthesis. Dysregulation in any of these pathways leads to diminished cellular lipoylation.
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