Sideroblastic Anemia

Bottomley, Sylvia S.; Fleming, Mark D.

doi:10.1016/j.hoc.2014.04.008

Cited by 95 publications

(33 citation statements)

References 87 publications

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“…Of interest was the data of three spherocytosis patients of whom ferrokinetic studies were available before and after splenectomy. We observed striking differences in plasma iron half-life before splenectomy (22, Notably, in congenital sideroblastic anemia, a disease characterized by disrupted utilization of iron in erythroblasts, ineffective erythropoiesis and relative low reticulocyte counts [24], half-life of iron was significantly longer than in other forms of non-transfusion-dependent hereditary anemia (63 ± 21 min versus 45 ± 23 min, 95% CI [4.5; 31.4], p = 0.02).…”

Section: Disappearance Half-life Of Transferrin-bound Is Shorter In Nmentioning

confidence: 99%

Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans

Vuren

Wijk

Beers

et al. 2020

IJMS

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Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of 59Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous 59Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40). Mean mucosal iron uptake and mucosal iron transfer (±SD) were elevated in patients with HH (59 ± 18%, 80 ± 15% respectively), HA (65 ± 17%, 74 ± 18%) and ID (84 ± 14%, 94 ± 6%) compared to healthy controls (43 ± 19%, 64 ± 18%) (p < 0.05) resulting in increased iron retention after 14 days compared to healthy controls in all groups (p < 0.01). The fraction of retained iron utilized for red cell production was 0.37 ± 0.17 in untreated HA, 0.55 ± 0.20 in untreated HH and 0.99 ± 0.22 in ID (p < 0.01). Interestingly, compared to red blood cell iron utilization after oral iron administration, red blood cell iron utilization was higher after injection of transferrin-bound iron in HA and HH. Liver iron retention was considerably higher in HH and HA compared to ID. We hypothesize that albumin serves as a scavenger of absorbed Fe(II) for delivering albumin-bound Fe(III) to hepatocytes.

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Section: Disappearance Half-life Of Transferrin-bound Is Shorter In Nmentioning

confidence: 99%

Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans

Vuren

Wijk

Beers

et al. 2020

IJMS

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“…Thus, mutations in genes responsible for porphyrin synthesis, such as ALAS2 (which encodes 5-aminolevulinic acid [ALA] synthase 2), lead to sideroblastic anemia. Mutations in genes involved in Fe-S clusters and mitochondrial tRNA metabolism are also associated with sideroblastic anemia (10,12), although the detailed molecular mechanisms of how defects in each gene result in abnormal mitochondrial iron accumulation remain unclear. In adults, this syndrome is commonly observed in association with myelodysplastic syndrome (MDS; MDS with ring sideroblasts is termed MDS-RS) (10,13).…”

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confidence: 99%

“…A recent study involving a large cohort revealed that SF3B1, a gene for a splicing factor, is frequently mutated in MDS-RS (13). Mutations in SF3B1 resulted in splicing errors of the ATP-binding cassette B7 (ABCB7) gene, which is involved in Fe-S cluster transport and is one of the causative genes of congenital sideroblastic anemia (CSA) (10,12,13).…”

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confidence: 99%

“…The most common type of CSA is X-linked sideroblastic anemia (XLSA), which is caused by defects in the X-linked gene ALAS2 (10,12,14). ALAS2 encodes an enzyme that catalyzes the rate-limiting step in heme biosynthesis in erythroid cells (10,12,14). This pathway converts glycine and acetyl coenzyme A (acetyl-CoA) to ALA and requires pyridoxal 5=-phosphate (PLP; vitamin B 6 ) as a cofactor (10,12,14).…”

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confidence: 99%

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Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation

Saito

Fujiwara

Hatta

et al. 2019

Molecular and Cellular Biology

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Ring sideroblasts are a hallmark of sideroblastic anemia, although little is known about their characteristics. Here, we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene, a gene responsible for X-linked sideroblastic anemia (XLSA). Although heterozygous female mice showed an anemic phenotype, ring sideroblasts were not observed in their bone marrow. We next established human induced pluripotent stem cell-derived proerythroblast clones harboring the same ALAS2 gene mutation. Through coculture with sodium ferrous citrate, mutant clones differentiated into mature erythroblasts and became ring sideroblasts with upregulation of metal transporters (MFRN1, ZIP8, and DMT1), suggesting a key role for ferrous iron in erythroid differentiation. Interestingly, holo-transferrin (holo-Tf) did not induce erythroid differentiation as well as ring sideroblast formation, and mutant cells underwent apoptosis. Despite massive iron granule content, ring sideroblasts were less apoptotic than holo-Tf-treated undifferentiated cells. Microarray analysis revealed upregulation of antiapoptotic genes in ring sideroblasts, a profile partly shared with erythroblasts from a patient with XLSA. These results suggest that ring sideroblasts exert a reaction to avoid cell death by activating antiapoptotic programs. Our model may become an important tool to clarify the pathophysiology of sideroblastic anemia.

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